Prosthetic mitral valve with improved anchors and seal

ABSTRACT

A method for replacing a native heart valve includes advancing a delivery catheter having a valve prosthesis disposed along a distal end portion thereof, wherein the valve includes an inner frame having an hourglass shape and an outer sealing frame connected to and surrounding the inner frame. A valve body is mounted within the inner frame and includes a plurality of leaflets. The leaflets have longitudinal curvatures when in an open position, wherein the curvatures are shaped for conforming to the curved interior surface of the inner frame. This combination of features reduces the possibility of blood stagnating between the leaflets and inner frame, which reduces the possibility of thrombus formation.

PRIORITY CLAIM AND INCORPORATION BY REFERENCE TO ANY PRIORITYAPPLICATIONS

This application is a continuation of U.S. application Ser. No.17/343,554, filed Jun. 9, 2021, which is a continuation of U.S.application Ser. No. 16/286,436, filed Feb. 26, 2019, now U.S. Pat. No.11,051,934, which claims the benefit of U.S. Provisional Application No.62/781,817, filed Dec. 19, 2018, and U.S. Provisional Application No.62/636,672, filed Feb. 28, 2018, the entirety of each of which is herebyincorporated by reference.

BACKGROUND Field

Certain embodiments disclosed herein relate generally to prostheses forimplantation within a lumen or body cavity. In particular, certainembodiments relate to expandable prostheses such as replacement heartvalves, such as for the mitral valve, that are configured to be securedto intralumenal tissue and prevent paravalvular leakage.

Description of the Related Art

Human heart valves, which include the aortic, pulmonary, mitral andtricuspid valves, function essentially as one-way valves operating insynchronization with the pumping heart. The valves allow blood to flowdownstream, but block blood from flowing upstream. Diseased heart valvesexhibit impairments such as narrowing of the valve or regurgitation,which inhibit the valves' ability to control blood flow. Suchimpairments reduce the heart's blood-pumping efficiency and can be adebilitating and life threatening condition. For example, valveinsufficiency can lead to conditions such as heart hypertrophy anddilation of the ventricle. Thus, extensive efforts have been made todevelop methods and apparatuses to repair or replace impaired heartvalves.

Prostheses exist to correct problems associated with impaired heartvalves. For example, mechanical and tissue-based heart valve prosthesescan be used to replace impaired native heart valves. More recently,substantial effort has been dedicated to developing replacement heartvalves, particularly tissue-based replacement heart valves that can bedelivered with less trauma to the patient than through open heartsurgery. Replacement valves are being designed to be delivered throughminimally invasive procedures and even percutaneous procedures. Suchreplacement valves often include a tissue-based valve body that isconnected to an expandable frame that is then delivered to the nativevalve's annulus.

These replacement valves are often intended to at least partially blockblood flow. However, a problem occurs when blood flows around the valveon the outside of the prosthesis. For example, in the context ofreplacement heart valves, paravalvular leakage has proven particularlychallenging. An additional challenge relates to the ability of suchprostheses to be secured relative to intralumenal tissue, e.g., tissuewithin any body lumen or cavity, in an atraumatic manner. Yet anotherchallenge arises when trying to reduce the likelihood of thrombosiswithin parts of the replacement valves.

SUMMARY

Embodiments of the present disclosure are directed to a prosthesis, suchas but not limited to a replacement heart valve. Further embodiments aredirected to delivery systems, devices and/or methods of use to deliverand/or controllably deploy a prosthesis, such as but not limited to areplacement heart valve, to a desired location within the body. In someembodiments, a replacement heart valve and methods for delivering areplacement heart valve to a native heart valve, such as a mitral valve,are provided.

In some embodiments, a delivery system and method are provided fordelivering a replacement heart valve to a native mitral valve location.The delivery system and method may utilize a transseptal approach. Insome embodiments, components of the delivery system facilitate bendingof the delivery system to steer a prosthesis from the septum to alocation within the native mitral valve. In some embodiments, a capsuleis provided for containing the prosthesis for delivery to the nativemitral valve location. In other embodiments, the delivery system andmethod may be adapted for delivery of implants to locations other thanthe native mitral valve.

The present disclosure includes, but is not limited to, the followingembodiments.

Embodiment 1: A mitral valve prosthesis configured to transition betweena compressed position and an expanded position, the prosthesis having aproximal end and a distal end, the prosthesis comprising an inner framecomprising a body comprising a plurality of circumferentially extendablestruts, and a plurality of longitudinally extending struts, wherein theplurality of circumferentially extendable struts and the plurality oflongitudinally extending struts form two or more rows of cells, and aplurality of inner frame anchoring features extending distally from thebody, wherein the inner frame is generally hourglass shaped in theexpanded position, an outer frame connected to the inner frame andcomprising a plurality of connected first v-shaped struts extendingaround a circumference of the prosthesis, and a plurality of separatesecond v-shaped struts, each of the separate second v-shaped strutsattached within each of the connected first v-shaped struts, a valvebody connected within an interior surface of the inner frame, the valvebody comprising a plurality of leaflets arranged to allow flow in afirst direction and prevent flow in a second direction opposite thefirst direction, wherein the leaflets conform to the interior surface ofthe inner frame when the valve body is in an open position for reducinga formation of thrombi between the plurality of leaflets and theinterior surface of the inner frame, and a fabric skirt connected to aninner surface of the outer frame and extending distally beyond a distalend of the outer frame, wherein the fabric skirt is adapted forcontacting a mitral annulus and forming a seal.

Embodiment 2: The mitral valve prosthesis of Embodiment 1, wherein theplurality of separate second v-shaped struts are thinner than theplurality of connected first v-shaped struts.

Embodiment 3: The mitral valve prosthesis of Embodiment 1 or Embodiment2, further comprising a stiffness improving material attached to theouter frame, the inner frame, and the plurality of inner frame anchoringfeatures, the stiffness improving material providing tension to theinner frame anchoring features when the prosthesis is in the expandedposition and not providing tension to the inner frame anchoring featureswhen the prosthesis is in the compressed position.

Embodiment 4: The mitral valve prosthesis of any one of Embodiments 1-3,wherein the plurality of inner frame anchoring features extend radiallyoutwardly and then proximally, wherein each of the plurality of innerframe anchoring features ends with an anchoring tip.

Embodiment 5: The mitral valve prosthesis of Embodiment 4, wherein adistal end of the outer frame is longitudinally spaced above each of theanchoring tips.

Embodiment 6: The mitral valve prosthesis of any one of Embodiments 1-5,wherein a distal end of the outer frame ends proximal to a distal end ofthe two or more rows of cells.

Embodiment 7: The mitral valve prosthesis of any one of Embodiments 1-6,wherein the inner frame comprises a mushroom tab at a proximal end of atleast one of the plurality of longitudinally extending struts.

Embodiment 8: The mitral valve prosthesis of any one of Embodiments 1-7,wherein the inner frame and the outer frame each comprise a plurality ofapertures at or near a proximal end of the inner frame and the outerframe, and wherein each of the plurality of apertures of the inner framegenerally aligns with an aperture of the plurality of apertures of theouter frame.

Embodiment 9: The mitral valve prosthesis of any one of Embodiments 1-8,wherein the outer frame comprises a plurality of outer frame anchoringfeatures extending radially outwards.

Embodiment 10: The mitral valve prosthesis of any one of Embodiments1-9, wherein the skirt is positioned between the inner frame and theouter frame.

Embodiment 11: The mitral valve prosthesis of any one of Embodiments1-11, further comprising a valve body positioned within an interior ofthe inner frame, the valve body comprising a plurality of leafletsconfigured to allow flow in a first direction and prevent flow in asecond opposite direction.

Embodiment 12: The mitral valve prosthesis of any one of Embodiments1-11, wherein the expandable replacement heart valve prosthesis isconfigured to act as a replacement mitral heart valve.

Embodiment 13: The mitral valve prosthesis of any one of Embodiments1-12, wherein each of the plurality of inner frame anchoring featuresends with a pair of L-shaped anchors, the pair of L-shaped anchors beingradially offset from one another.

Embodiment 14: The mitral valve prosthesis of any one of Embodiments1-13, wherein the outer frame comprises a plurality of proximallyextending struts extending between connections of adjacent connectedfirst v-shaped struts.

Embodiment 15: The mitral valve prosthesis of Embodiment 14, wherein theouter frame comprises a circumferential shoulder spaced from a proximalend and a distal end of the outer frame, the circumferential shoulderbeing the radially outermost portion of the outer frame.

Embodiment 16: The mitral valve prosthesis of Embodiment 16, wherein theproximally extending struts are spaced radially inwards from thecircumferential shoulder, and wherein a distal end of each of theplurality of first v-shaped struts is spaced radially inwards from thecircumferential shoulder.

Embodiment 17: The mitral valve prosthesis of any one of Embodiments1-16, wherein the expandable replacement heart valve prosthesiscomprises nine inner frame anchoring features.

Embodiment 18: A delivery assembly configured to delivery an expandablereplacement heart valve prosthesis, the delivery assembly comprising asteerable delivery system configured to releasably retain the expandablereplacement heart valve prosthesis in a compressed position, and theexpandable replacement heart valve prosthesis configured to expandablebetween the compressed position and an expanded position, the prosthesiscomprising an inner frame comprising a plurality of circumferentiallyextendable struts, a plurality of longitudinal extending struts, and aplurality of inner frame anchoring features, wherein the inner frame isgenerally hourglass shaped in the expanded position, and an outer frameconnected to the inner frame and comprising a plurality of connectedfirst v-shaped struts extending around a circumference of theprosthesis, wherein the steerable delivery system is configured tosequentially expand portions of the prosthesis from the compressedposition to the expanded position.

Embodiment 19: The delivery assembly of Embodiment 18, wherein the outerframe further comprises a plurality of separate second v-shaped struts,each of the separate second v-shaped struts attached within each of theconnected first v-shaped struts.

Embodiment 20: The delivery assembly of Embodiment 18 or Embodiment 19,wherein the steerable delivery system further comprises an anchorseparator comprising a body, a plurality of extensions extendingradially away from the body, the plurality of extensions forming aplurality of longitudinally extending grooves, each of the plurality oflongitudinally extending grooves configured to receive one of theplurality of inner frame anchoring features in the compressed position,and a lumen longitudinally extending through the body, wherein the bodyand the plurality of extensions are radially inwardly tapered at aproximal end and distal end of the anchor separator.

Embodiment 21: An expandable replacement heart valve prosthesis. Theprosthesis can be configured to transition between a compressed positionand an expanded position. The prosthesis can comprise an inner frame.The inner frame can comprise a plurality of circumferentially extendablestruts. The inner frame can comprise a plurality of longitudinallyextending struts. The plurality of circumferentially extendable strutsand the plurality of longitudinally extending struts can form two ormore rows of cells. The inner frame can comprise a plurality of innerframe anchoring features. The inner frame can be generally hourglassshaped in the expanded position. The prosthesis can comprise an outerframe. The outer frame can be connected to the inner frame. The outerframe can comprise a plurality of connected first v-shaped struts. Theplurality of connected first v-shaped struts can extend around acircumference of the prosthesis. The outer frame can comprise aplurality of separate second v-shaped struts. Each of the separatesecond v-shaped struts can be attached within each of the connectedfirst v-shaped struts. The plurality of separate second v-shaped strutscan be thinner than the plurality of connected first v-shaped struts.The prosthesis can comprise a stiffness improving material attached tothe outer frame. The stiffness improving material can be attached to theinner frame. The stiffness improving material can be attached to theplurality of inner frame anchoring features. The stiffness improvingmaterial can provide tension to the inner frame anchoring features whenthe prosthesis is in the expanded position. The stiffness improvingmaterial may not providing tension to the inner frame anchoring featureswhen the prosthesis is in the compressed position.

Embodiment 22: The prosthesis of Embodiment 21, wherein the stiffnessimproving material can comprise sutures, fabric, or cloth.

Embodiment 23: The prosthesis of Embodiments 21-22, wherein the outerframe can comprise a plurality of outer frame anchoring features.

Embodiment 24: The prosthesis of Embodiments 21-23, wherein theprosthesis can be configured for use as a replacement mitral valve.

Embodiment 25: The prosthesis of any one of Embodiments 21-24, whereinthe prosthesis can comprise a skirt positioned between the inner frameand the outer frame. The skirt can be configured to automatically tuckwithin cells in the outer frame when the prosthesis is compressed.

Embodiment 26: The prosthesis of any one of Embodiments 21-25, whereinthe prosthesis can comprise a valve body. The valve body can bepositioned within an interior of the first frame. The valve body cancomprise a plurality of leaflets configured to allow flow in a firstdirection and prevent flow in a second opposite direction.

Embodiment 27: An expandable replacement heart valve prosthesisconfigured to transition between a compressed position and an expandedposition, wherein the inner frame can comprise a generally cylindricalfirst frame and an inwardly curved secondary frame located within thegenerally cylindrical first frame and attached to the generallycylindrical first frame, the inwardly curved secondary frame forming agenerally hourglass shape within a longitudinal lumen of the innerframe.

Embodiment 28: The prosthesis of Embodiment 27, wherein the secondaryframe can comprise a plurality of longitudinal struts on an outersurface of a fabric component.

Embodiment 29: The prosthesis of Embodiment 27, wherein the secondaryframe can comprise a balloon filled with fluid.

Embodiment 30: The prosthesis of Embodiment 27, wherein the secondaryframe can comprise a swellable material.

Embodiment 31: The prosthesis of any one of Embodiments 21-26,comprising the features of any one of Embodiments 27-30.

Embodiment 32: The prosthesis of any one of Embodiments 21-31, whereineach of the plurality of inner frame anchoring features can end with apair of L-shaped anchors, the pair of L-shaped anchors being radiallyoffset from one another.

Embodiment 33: A delivery system configured to deliver a prosthesiscomprising a plurality of anchors, including any of the prosthesesdescribed herein this specification. The delivery system comprises ananchor separator comprising a body, a plurality of extensions extendingradially away from the body, the plurality of extensions forming aplurality of longitudinally extending grooves for receiving the anchorsof the prosthesis, and a lumen longitudinally extending through thebody. The body and the plurality of extensions are radially inwardlytapered at a proximal end and distal end of the anchor separator.

Embodiment 34: An expandable replacement heart valve prosthesis. Theprosthesis can be configured to transition between a compressed positionand an expanded position. The prosthesis can comprise a frame. The framecan have an inlet side. The frame can have a middle portion. The framecan have an outlet side. The frame can decrease in diameter at leastfrom the inlet side to the middle portion. The prosthesis can comprise avalve body comprising a plurality of leaflets positioned within theframe. Each of the valve leaflets can have an inlet end positioned alongthe decreasing diameter portion of the frame.

Embodiment 35: The prosthesis of Embodiment 34, wherein the frame can bean hourglass shape.

Embodiment 36: An expandable replacement heart valve prosthesis. Theprosthesis can be configured to transition between a compressed positionand an expanded position. The prosthesis can comprise an inner frame.The inner frame can comprise a plurality of inner frame anchoringfeatures. The features can extend from a lower portion of the innerframe. The prosthesis can comprise an outer frame. The outer frame canbe connected to the inner frame. The prosthesis can comprise a stiffnessimproving material. The material attached to the outer frame. Thematerial attached to the inner frame. The material attached to theplurality of inner frame anchoring features. The stiffness improvingmaterial can provide tension to the inner frame anchoring features whenthe prosthesis is in the expanded position. The material may not providetension to the inner frame anchoring features when the prosthesis is inthe compressed position.

Embodiment 37: The prosthesis of Embodiment 36, wherein the inner frameanchoring features can comprise a plurality of anchors. The anchors canextend radially outward from the inner frame. The anchors can extendgenerally toward an upper portion of the inner frame.

Embodiment 38: The prosthesis of any one of Embodiments 36 or 37,wherein the outer frame can extend over the inner frame.

Embodiment 39: The prosthesis of any one of Embodiments 36-38, whereinthe stiffness improving material can comprise suture, fabric, or clothmaterial. The material can extend from a lower portion of the outerframe. The material can attach to the inner frame anchoring features.The material can attach to a lower portion of the inner frame.

Embodiment 40: An expandable replacement heart valve prosthesis. Theprosthesis can be configured to transition between a compressed positionand an expanded position. The prosthesis can comprise a frame. The framecan comprise a plurality of connected first v-shaped struts. The strutscan extend around a circumference of the prosthesis. The frame cancomprise a plurality of separate second v-shaped struts. Each of theseparate second v-shaped struts can be attached within each of theconnected first v-shaped struts. The plurality of separate secondv-shaped struts can be thinner than the plurality of connected firstv-shaped struts.

Embodiment 41: An expandable replacement heart valve prosthesis. Theprosthesis can be configured to transition between a compressed positionand an expanded position. The prosthesis can comprise a frame. The framecan comprise a plurality of circumferentially extendable struts. Theframe can comprise a plurality of longitudinally extending struts. Theplurality of circumferentially extendable struts and the plurality oflongitudinally extending struts can form two or more rows of cells.

Embodiment 42: A frame which can comprise a cell pattern as shown anddescribed in FIGS. 3, 4 and/or 5A.

Embodiment 43: A prosthesis comprising one or more features of theforegoing description.

Embodiment 44: A method of treating valve insufficiency comprising oneor more features of the foregoing description.

Embodiment 45: A delivery system for delivering the prosthesiscomprising one or more features of the foregoing description.

Embodiment 46: The mitral valve prosthesis of any one of Embodiments1-17, wherein free edges of a distal end of each of the plurality ofleaflets are spaced away from the inner frame.

Embodiment 47: The mitral valve prosthesis of any one of Embodiments1-17 and 46, wherein the fabric skirt is connected to an outer surfaceof a distal end of the inner frame, and wherein the fabric skirt is heldin tension between the outer frame and the inner frame.

Embodiment 48: The mitral valve prosthesis of any one of Embodiments1-17 and 46-47, wherein the fabric skirt has sufficient flexibility toconform against a mitral annulus.

Embodiment 49: A mitral valve prosthesis configured to transitionbetween a compressed position and an expanded position, the prosthesishaving a proximal end and a distal end, the prosthesis comprising aninner frame comprising a body comprising a plurality ofcircumferentially extendable struts, and a plurality of longitudinallyextending struts, wherein the plurality of circumferentially extendablestruts and the plurality of longitudinally extending struts form two ormore rows of cells, and a plurality of inner frame anchoring featuresextending distally from the body, wherein the inner frame is generallyhourglass shaped in the expanded position, an outer frame connected tothe inner frame and comprising a plurality of connected first v-shapedstruts extending around a circumference of the prosthesis, and aplurality of separate second v-shaped struts, each of the separatesecond v-shaped struts attached within each of the connected firstv-shaped struts, a valve body connected within an interior surface ofthe inner frame, the valve body comprising a plurality of leafletsarranged to allow flow in a first direction and prevent flow in a seconddirection opposite the first direction, and a fabric skirt connected toan inner surface of the outer frame and an outer surface of a distal endof the inner frame under tension, wherein the fabric skirt extendsdistally beyond a distal end of the outer frame, and wherein the fabricskirt is adapted for conforming against a mitral annulus.

Embodiment 50: A mitral valve prosthesis configured to transitionbetween a compressed position and an expanded position, the prosthesishaving a proximal end and a distal end, the prosthesis comprising aninner frame comprising a body comprising a plurality ofcircumferentially extendable struts, and a plurality of longitudinallyextending struts, wherein the plurality of circumferentially extendablestruts and the plurality of longitudinally extending struts form two ormore rows of cells, and a plurality of inner frame anchoring featuresextending distally from the body, wherein the inner frame is generallyhourglass shaped in the expanded position, an outer frame connected tothe inner frame and comprising a plurality of connected first v-shapedstruts extending around a circumference of the prosthesis, and aplurality of separate second v-shaped struts, each of the separatesecond v-shaped struts attached within each of the connected firstv-shaped struts.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other features, aspects and advantages are described belowwith reference to the drawings, which are intended to illustrateembodiments of prostheses including embodiments of various components ofthese prostheses.

FIG. 1 illustrates an embodiment of a multi-portion replacementprosthesis.

FIG. 2 illustrates an embodiment of an inner frame of the multi-portionreplacement prosthesis shown in FIG. 1.

FIG. 3 illustrates a flat pattern of an embodiment of the inner frameshown in FIG. 2.

FIG. 4 illustrates a portion of the inner frame of FIG. 2.

FIGS. 5A-5E illustrate an inner frame having an hourglass shape.

FIGS. 5F-5I illustrate leaftlets opening in a frame having an hourglassshape such as shown in FIGS. 5A-5E.

FIGS. 5J-5K illustrate a cross section of leaftlets in open and closedpositions in a frame having an hourglass shape such as shown in FIGS.5A-5E.

FIGS. 6A-6D illustrate an embodiment of an outer frame of themulti-portion replacement prosthesis shown in FIG. 1.

FIG. 7A illustrates a flat pattern of the outer frame of FIG. 6 in acompressed configuration.

FIG. 7B illustrates a flat pattern of the outer frame of FIG. 6 in anexpanded configuration.

FIGS. 7C-7D illustrate alternate embodiments of a flat pattern of anouter frame.

FIGS. 8A-8B illustrate alternative flat patterns for an outer frame.

FIGS. 9-11 illustrate a multi-portion replacement prosthesis with anouter skirt.

FIG. 12 illustrate a multi-portion replacement prosthesis having outerframe anchoring features.

FIGS. 13A-13B illustrate auto-tucking features of embodiments of thedisclosed prosthesis.

FIGS. 14A-14B illustrate an embodiment for improving inner frameanchoring feature stiffness.

FIG. 15 illustrates an alternate embodiment for improving inner frameanchoring feature stiffness.

FIG. 16 illustrates assessment of prosthesis function prior to release.

FIGS. 17A-17B illustrate an embodiment of replacement prosthesis.

FIGS. 18A-20 illustrate an embodiment of an alternative replacementprosthesis.

FIG. 21 illustrates an embodiment of a replacement prostheses.

FIG. 22 shows an embodiment of an inner frame of an alternatereplacement prosthesis.

FIG. 23 shows an embodiment of an outer frame of an alternatereplacement prosthesis.

FIG. 24 show an embodiment of anchoring elements.

FIGS. 25A-25B illustrate embodiments of an anchor separator.

FIG. 26 illustrates an embodiment of an anchor separator within a frameof a replacement prosthesis.

FIGS. 27A-27B show and embodiment of an anchor separator in use with areplacement prosthesis.

FIGS. 28A-28B show an embodiment of a suturing system for attachment toa delivery system.

FIG. 29 is an embodiment of an alternative replacement prosthesis.

FIGS. 30A-30D illustrates an embodiment of a multi-portion replacementprosthesis.

FIG. 31 illustrates an alternate embodiment of an inner frame with asecondary inner frame having an hourglass shape.

FIG. 32 illustrates a schematic representation of a transseptal deliveryapproach.

FIG. 33 illustrates a schematic representation of a valve prosthesispositioned within a native mitral valve.

FIG. 34 illustrates a schematic representation of a valve prosthesispositioned within a native mitral valve.

FIG. 35 shows an embodiment of a delivery system for use with any of theprostheses disclosed herein.

DETAILED DESCRIPTION

The present specification and drawings provide aspects and features ofthe disclosure in the context of several embodiments of prostheses,replacement heart valves, and methods that are configured for use in thevasculature of a patient, such as for replacement of natural heartvalves in a patient. These embodiments may be discussed in connectionwith replacing specific valves such as the patient's mitral valve.However, it is to be understood that the features and concepts discussedherein can be applied to replacing other types of valves including, butnot limited to, the aortic valve, the pulmonary valve, and the tricuspidvalve. Moreover, it is to be understood that the features and conceptsdiscussed herein can be applied to products other than heart valveimplants. For example, the controlled positioning, deployment, and/orsecuring features described herein can be applied to medical implants,for example other types of expandable prostheses, for use elsewhere inthe body, such as within a vein, or the like. In addition, particularfeatures of a prosthesis should not be taken as limiting, and featuresof any one embodiment discussed herein can be combined with features ofother embodiments as desired and when appropriate.

Certain terminology may be used in the following description for thepurpose of reference only, and thus are not intended to be limiting. Forexample, terms such as “upper”, “lower”, “upward”, “downward”, “above”,“below”, “top”, “bottom” and similar terms refer to directions in thedrawings to which reference is made. Terms such as “proximal”, “distal”,“radially outward”, “radially inward”, “outer”, “inner”, and “side”,describe the orientation and/or location of portions of the componentsor elements within a consistent but arbitrary frame of reference whichis made clear by reference to the text and the associated drawingsdescribing the components or elements under discussion. Such terminologymay include the words specifically mentioned above, derivatives thereof,and words of similar import. Similarly, the terms “first”, “second”, andother such numerical terms referring to structures neither imply asequence or order unless clearly indicated by the context.

In some embodiments, the term “proximal” may refer to the parts of theprostheses, or components thereof, which are located closer to theoperator of the device and system (e.g., the clinician implanting theprosthesis). The term “distal” may refer to the parts of the prostheses,or components thereof, which are located further from the operator ofthe device and system (e.g., the clinician implanting the prosthesis).However, it is to be understood that this terminology may be reverseddepending on the delivery technique utilized (e.g., a transapicalapproach as compared to a transseptal approach). In some situations, theprosthesis, or components thereof, may be oriented such that an upperend is a proximal portion and a lower end is a distal portion.

In some situations, the prosthesis, or components thereof, the upper endmay be an inflow end and the lower end may be an outflow end. Forexample, a valve body used with the prosthesis can allow flow from theupper end to the lower end. However, it is to be understood that theinflow end and the outflow end may be reversed. For example, the valvebody used with the prosthesis can allow flow from the lower end to theupper end.

A longitudinal axis of the prosthesis, or components thereof, may bedefined as the central axis that extends through the center of theprosthesis or component between the upper and lower ends of theprosthesis or component (e.g., the prosthesis, the outer frame, and/orthe inner frame). The prostheses described herein may be replacementvalves that can be designed to replace a damaged or diseased nativeheart valve such as a mitral valve, as discussed above. It should beunderstood that the prostheses are not limited to being a replacementvalve.

As will be described in further detail below, the prostheses can includean inner frame and/or an outer frame or an inner portion and/or an outerportion. In some embodiments, the inner frame can be a valve framedesigned to support a valve body. In some embodiments, the outer framecan be a sealing frame designed to form a seal about a periphery of theouter frame. For example, the outer frame can engage tissue of a bodycavity about a periphery of the outer frame and form a seal with saidtissue. In some embodiments described herein, the outer frame can beattached to the inner frame at one or more stationary couplings suchthat the outer frame is fixed to the inner frame at one or morelocations. It is to be understood that the outer frame can be attachedto the inner frame via one or more movable couplings such as, but notlimited to, rails. This can beneficially allow the outer frame to beadjusted relative to the inner frame to better conform to the anatomy ofa patient's body cavity.

The inner frame and/or outer frame may be described as having an upperregion, an intermediate region, and a lower region. In some situations,such as those in which the prostheses are positioned within a nativemitral valve, the upper region can be generally positionedsupra-annularly (i.e., above the plane of the annulus), the intermediateregion can be generally positioned intra-annularly (i.e., within theplane of the annulus), and the lower region can be positionedsub-annularly (i.e., below the plane of the annulus). However, it is tobe understood that in some situations, the positioning of the innerframe and/or outer frame relative to the annulus can differ. Moreover,it is to be understood that in some embodiments, the inner frame and/orouter frame can omit one or more of the upper region, the intermediateregion, and/or the lower region.

While certain combinations of inner frames and outer frames aredescribed herein, it is to be understood that the inner frames and outerframes can be interchanged. This can beneficially allow the prosthesisto be configured in a manner which better suits the native anatomy ofthe patient. Moreover, while the inner frames and outer frames can beattached prior to delivery into the patient, it is to be understood thatthe inner frames and outer frames can be delivered separately into thepatient and subsequently attached in the patient's body. This canbeneficially reduce the crimp profile when delivering the frames to thebody cavity. The prostheses described herein can be used as a standalonedevice. For example, the prosthesis can be deployed at a native mitralvalve and be sized and shaped appropriately to replace the function ofthe native mitral valve. However, it is to be understood that theprostheses described herein can be used with other devices. For example,one or more clips can be used to hold together native leaflets of aheart valve. This can advantageously allow a smaller prosthesis to beutilized at the native mitral valve.

Embodiments of Replacement Valves and Frames

FIG. 1 shows an embodiment of the frame of a multi-portion prosthesis100 in an expanded configuration. The prosthesis 100 can include, butare not limited to, an inner frame 120, an outer frame 140, a valve body160 (shown in FIGS. 9-11), and a skirt 180 (also shown in FIGS. 9-11). Alongitudinal axis of the prosthesis 100 may be defined as the centralaxis that extends through the center of the prosthesis 100 between theupper and lower ends of the prosthesis 100. In some situations, theprosthesis 100 may be oriented such that an upper end of the prosthesis100 is a proximal portion and a lower end of the prosthesis 100 is adistal portion. The illustrated prosthesis 100, as well as otherprostheses described herein, may include components which areself-expanding or balloon expandable. For example, in some embodiments,the inner frame 120 and/or outer frame 140 can be self-expanding. Theprosthesis 100, as well as other prostheses described herein, may be areplacement valve that can be designed to replace a damaged or diseasednative heart valve such as a mitral valve, as discussed above. It shouldbe understood that the prosthesis 100, as well as other prosthesesdescribed herein, are not limited to being a replacement valve.

Embodiments of the disclosed prosthesis 100 may have a reduced crimpinner diameter (ID), such as 25 Fr, 24 Fr, 23 Fr, 22 Fr, 21 Fr, or 20Fr. Embodiments of the disclosed prosthesis 100 may have a reduced crimpID, such as less than 25 Fr, 24 Fr, 23 Fr, 22 Fr, 21 Fr, or 20 Fr.Embodiments of the disclosed prosthesis 100 may have a reduced crimp ID,such as greater than 25 FR, 24 Fr, 23 Fr, 22 Fr, 21 Fr, or 20 Fr. Insome embodiments, the prosthesis 100 may have a crimp length of 48, 47,46, 45, 44, 43, 42, 41, or 40 mm. In some embodiments, the prosthesis100 may have a crimp length of less than 48, 47, 46, 45, 44, 43, 42, 41,or 40 mm. In some embodiments, the prosthesis 100 may have a crimplength of greater than 48, 47, 46, 45, 44, 43, 42, 41, or 40 mm. In someembodiments, the prosthesis 100 may only require retrieval forces of 60,55, 50, 45, or 40 lbs. to compress the prosthesis 100. In someembodiments, the prosthesis 100 may only require retrieval forces ofless than 60, 55, 50, 45, or 40 lbs. to compress the prosthesis 100. Insome embodiments, the prosthesis 100 may only require retrieval forcesof greater than 60, 55, 50, 45, or 40 lbs. to compress the prosthesis100.

As further disclosed below, the multi-portion prosthesis 100 can be madeof one or more frames, such as one, two, or three frames. In someembodiments, the prosthesis 100 can be a dual-frame design, having aninner and an outer frame. In some embodiments, the inner and outer frameare integrally formed into one frame. In other embodiments, the framescan be separate and connected together.

Inner Frame

FIG. 2 illustrates the inner frame 120 of the prosthesis 100 with theouter frame 140 removed for clarity. Further, FIG. 3 illustrates a flatpattern of the inner frame 120. The inner frame 120 can generallyinclude an inner frame body 122 and an inner frame anchoring feature 124(if used in a mitral valve, also known as a ventricular or distalanchor). The inner frame body 122 can have an upper region 126, anintermediate region 128, and a lower region 130. As shown, the innerframe body 122 can have a generally cylindrical shape such that thediameters of the upper region 126, the intermediate region 128, and thelower region 130 are generally equivalent. However, it is to beunderstood that the diameters of the upper region 126, the intermediateregion 128, and/or the lower region 130 can be different, such as thehourglass shape discussed below with respect to FIGS. 5A-5E. Forexample, in some embodiments, a diameter of the intermediate region 128can be larger/smaller than the upper region 126 and the lower region 130such that the frame body 122 has a generally bulbous shape. In someembodiments, the diameter of the lower region 130 can be larger than thediameter of the upper region 126. In other embodiments, the diameter ofthe upper region 126 can be larger than the diameter of the lower region130. Moreover, although the inner frame body 122 has been described andillustrated as being cylindrical or having circular cross-sections, itis to be understood that all or a portion of the inner frame body 122can have a non-circular cross-section such as, but not limited to, aD-shape, an oval or an otherwise ovoid cross-sectional shape.

In some situations, such as those in which the prosthesis 100 ispositioned within a native mitral valve, the upper region 126 can begenerally positioned supra-annularly (i.e., above the plane of theannulus), the intermediate region 128 can be generally positionedintra-annularly (i.e., within the plane of the annulus), and the lowerregion 130 can be positioned sub-annularly (i.e., below the plane of theannulus). However, it is to be understood that in some situations, thepositioning of the inner frame 120 relative to the annulus can differ.For example, the intermediate region 128 can be positionedsupra-annularly. Moreover, it is to be understood that in someembodiments, the inner frame 120 can omit one or more of the upperregion 126, the intermediate region 128, and/or the lower region 130.

As shown FIG. 2, the inner frame 120 can include inner frame anchoringfeature(s) 124 (in some embodiments ventricular anchors) which canextend generally downwardly and/or radially outwardly at or proximate alower end of the lower region 130 of the inner frame body 122. The innerframe anchoring feature 124 can extend upwardly towards the upper region126 after extending radially outwards. As will be discussed in furtherdetail below, components of the inner frame 120, such as the inner frameanchoring feature 124, can be used to attach or secure the prosthesis100 to a native valve. For example, in some situations, the inner frameanchoring feature 124 can be used to attach or secure the prosthesis 100to a native mitral valve. In such an embodiment, the inner frameanchoring feature 124 can be positioned to contact or engage a nativemitral valve annulus on a ventricular side, tissue beyond the nativevalve annulus on a ventricular side, native leaflets on a ventricularside, and/or other tissue at or around the implantation location duringone or more phases of the cardiac cycle, such as systole and/ordiastole. When positioned within the native mitral valve, the innerframe anchoring feature 124 can beneficially eliminate, inhibit, orlimit upward movement of the prosthesis 100 when subject to upwardlydirected forces such as those which are applied on the prosthesis 100during systole. As shown, the prosthesis 100 can have nine inner frameanchoring features 124, but in some embodiments may have more or less,such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 inner frame anchoringfeatures 124.

With continued reference to the inner frame 120 illustrated in FIG. 2,the inner frame anchoring feature 124 can have ends or tips 124 apositioned radially outwardly relative to the longitudinal axis of theprosthesis 100. The inner frame anchoring feature 124 can extend at orproximate a lower end of the lower region 130 of the inner frame body122. As shown, the inner frame anchoring feature 124 can be formed froma plurality of individual anchors extending from the frame body 122. Theanchors can extend downwardly from one or more attachment points to theframe body 122 including, but not limited to, lower apices of cells 134b. The anchors can bend to extend generally radially outwardly of thelongitudinal axis of the prosthesis 100. As shown in the illustratedembodiment, the anchors can extend upwardly towards an end or tip 124 a.

As shown in the illustrated embodiment, the tips or ends 124 a extendupwardly in a direction parallel or generally parallel to thelongitudinal axis of the prosthesis 100. In some embodiments, the tip orend 124 a of anchoring feature 124 can extend generally perpendicular tothe longitudinal axis of the prosthesis 100. This can beneficiallyincrease the tissue contact area of the tip 124 a of the anchor. Thisincreased tissue contact area can beneficially reduce the stress appliedby the tip 124 a to tissue thereby reducing the amount of pressure andpotential for trauma to the tissue. In some embodiments, the tip or ends124 a of the anchoring feature 124 extend radially inward towards thelongitudinal axis and/or radially outward away from the longitudinalaxis.

The tips or ends 124 a as described above can advantageously provideatraumatic surfaces that may be used to contact or engage intralumenaltissue without causing unnecessary or undesired trauma to tissue. Forexample, the tips or ends 124 a can form flat, substantially flat,curved or other non-sharp surfaces to allow the tips to engage and/orgrasp tissue, without necessarily piercing or puncturing through tissue.A looped end or looped anchor, such as shown in FIG. 5A, may assist theframe in not getting caught up on structures at or near the treatmentlocation. For example, each loop can be configured so that when theprosthesis 100 is deployed in-situ and the anchoring features 124 aexpands away from the frame bodies 122, the movement of each loop from adelivered position to a deployed position avoids getting caught on thepapillary muscles. In some embodiments, the inner frame anchoringfeature 124 can include a lacrosse-head-shaped tip or end 124 a. In someembodiments, the tips or ends 124 a of the inner frame 120 may have asplit design such as shown in FIG. 24.

The anchoring features 124 can include nine individual anchors; however,it is to be understood that a greater number or lesser number ofindividual anchors can be used. For example, the number of individualanchors can be chosen as a multiple of the number of commissures for thevalve body 160 (shown in FIG. 10). As such, for a prosthesis 100 with avalve body 160 having three commissures, the inner frame anchoringfeature 124 can have three individual anchors (1:1 ratio), sixindividual anchors (2:1 ratio), nine individual anchors (3:1 ratio),twelve individual anchors (4:1 ratio), fifteen individual anchors (5:1ratio), or any other multiple of three. It is to be understood that thenumber of individual anchors need not correspond to the number ofcommissures of the valve body 160. Moreover, while the prosthesis 100includes anchoring features 124 with twelve anchors each, it is to beunderstood that a greater number of anchors or a lesser number ofanchors can be used.

With reference to the inner frame 120 illustrated in FIGS. 9-11 and 17B,the inner frame anchoring feature 124 can include covers and/or cushions138 to surround or partially surround at least a portion of the innerframe anchoring feature 124, such as the tips or ends 124 a. The coversand/or cushions 138 can be similar to those described in U.S.Publication No. 2015/0328000, which is incorporated by reference hereinin its entirety. The covers and/or cushions 138 can either fit snugglyaround the tips 124 a of the inner frame anchoring feature 124 or canhave extra padding so that the covers extend radially away from theinner frame body 122. As shown in the illustrated embodiment, coversand/or cushions 138 are attached to a subset of anchors of the innerframe anchoring feature 124 such that a cover and/or cushion 138 is usedon every third anchor. In some embodiments, the outer frame anchoringfeature 144 can include covers and/or cushions to surround or partiallysurround at least a portion of the outer frame anchoring feature 144,such as the tips or ends 144 a.

It is to be understood that greater or fewer numbers of covers and/orcushions 138 can be used with anchors of the inner frame anchoringfeature 124. For example, a cover and/or cushion 138 can be used onevery other anchor such that there is a 1:2 ratio of covers and/orcushions 138 to anchors. As another example, a cover and/or cushion 138can be used on every anchor (as shown in FIGS. 9-11). In someembodiments, all of the anchors can have the covers and/or cushions withsome of the anchors having less cushioning than others. In someembodiments, all of the anchors can have the padded covers. In otherembodiments, all of the anchors can have the snuggly fitting cushions.

The cover and/or cushion 138 can be formed from a deformable material.When the top portion of the cover and/or cushion 138 is subject topressure due to a downwardly directed force, the cover and/or cushion138 can compress and expand laterally outward. Such a force may beexerted upon the cover and/or cushion 138 when the cover and/or cushion138, for example, when the cover and/or cushion 138 contacts aventricular side of the mitral valve annulus during systole. Thecompression and lateral expansion of cover and/or cushion 138 canincrease the surface area of the cover and/or cushion 138 in contactwith the tissue, thereby exerting less pressure on the tissue andreducing the potential for trauma.

The inner frame 120 can be formed from many different materialsincluding, but not limited to a shape-memory metal such as Nitinol. Theinner frame 120 can be formed from a plurality of struts forming opencells, discussed below. In some embodiments, the inner frame 120 canhave a relatively rigid construction as compared to other components ofthe prosthesis 100 including, but not limited to, the outer frame 140.This can be achieved, for example, by the dimensions of the struts andby the configuration of the struts. The relatively rigid constructioncan more strongly resist deformation when subject to stress. This can bebeneficial during certain portions of the cardiac cycle, such assystole, during which the inner frame 120 may be subject to significantstresses on the inner frame anchoring feature 124. The relatively rigidconstruction can also be beneficial when a valve body 160 is positionedwithin the inner frame 120 to maintain the shape of the valve body 160.Moreover, the relatively rigid construction can be beneficial when theinner frame 120 is used for a valve-in-valve procedure wherein asupplemental prosthesis is positioned within the inner frame 120.However, although the inner frame 120 has been described as having arelatively rigid construction, it is to be understood that in someembodiments the inner frame 120 can have a construction relativelyflexible construction. For example, the inner frame 120 can have aconstruction which is about as flexible as, or more flexible than, othercomponents of the prosthesis 100, such as the outer frame 140.

The diameter of the upper region 126, intermediate region 128, and/orlower region 130 of the inner frame body 122 may be chosen such that theinner frame body 122 is adequately spaced from the body cavity when theprosthesis 100 is positioned within the body cavity. For example, inembodiments where the prosthesis 100 is positioned within the nativemitral valve, the inner frame body 122 may have a diameter which is lessthan the diameter of the native mitral valve annulus. In situationswhere the native mitral valve annulus is about 40 mm in diameter, thediameter of the inner frame body 122 can be about 30 mm. Accordingly,the diameter of the inner frame body 122 may be about 75% of thediameter of the native mitral valve annulus.

In some embodiments, the diameter of the inner frame body 122 may bebetween about 40% to about 90% of the diameter of the native valveannulus, between about 60% to about 85%, of the diameter of the nativevalve annulus, between about 70% to about 80% of the diameter of thenative valve annulus, any other sub-range between these ranges, or anyother percentage as desired. In some embodiments, the diameter of theinner frame body 122 can be in the range of about 20 mm to about 40 mmwhen expanded, in the range of about 25 mm to about 35 mm when expanded,in the range of about 28 mm to about 32 mm when expanded, any othersub-range within these ranges when expanded, or any other diameter whenexpanded as desired. Although the inner frame body 122 has beendescribed and illustrated as being cylindrical or having circularcross-sections, it is to be understood that all or a portion of theinner frame body 122 can be have a non-circular cross-section such as,but not limited to, a D-shape, an oval or an otherwise ovoidcross-sectional shape.

In other embodiments, the diameter of portions of the inner frame body122 such as the upper region 126, intermediate region 128, and/or lowerregion 130 may be chosen such that the inner frame body 122 ispositioned at the periphery of the body cavity. For example, inembodiments where the prosthesis 100 is positioned within the nativemitral valve, the inner frame body 122 may have a diameter which isabout equal to the diameter of the native mitral valve annulus.

FIG. 4 illustrates a portion of the inner frame body 122. As shown, theinner frame body 122 can include a plurality of struts with at leastsome of the struts forming cells 134 a-b. Any number of configurationsof struts can be used, such as rings of undulating struts shown formingellipses, ovals, rounded polygons, and teardrops, but also chevrons,diamonds, curves, and various other shapes. The upper row of cells 134 aand the lower row of cells 134 b can have a diamond/parallelogram orgenerally diamond/parallelogram shape. The rows of cells 134 a-b can beformed via a combination of struts. As shown in the illustratedembodiment, the upper row of cells 134 a can be formed from a first setof circumferentially-expansible struts 136 a at the top and bottom and alongitudinally extending strut 138. The lower row of cells 136 b can beformed from the second set of circumferentially-expansible struts 136 bon the top and bottom and a longitudinally extending strut 138 on eachside, which can be a continuation of the longitudinally extending strutmentioned above. As shown, the upper row of cells 134 a and the lowerrow of cells 136 b can share one circumferentially-expansible strut. Forexample, the bottom strut of the upper row of cells 134 a and the topstrut of lower row of cells 136 b may be shared. The first and secondsets of struts 136 a-b can have a zig-zag or undulating shape forming arepeating “V” shape. While the struts 136 a-b are generally describedand illustrated as being straight segments, it is to be understood thatsome or all of the struts 136 a-b may not form entirely straightsegments. For example, the struts 136 a-b can include some curvaturesuch that the upper and/or lower apices are curved as shown in FIG. 2.

Further, as shown in FIG. 4 the longitudinally extending strut 138 cangenerally extend from a bottom of the inner frame body 122 to a top ofthe inner frame body 122. Advantageously, the longitudinally extendingstrut 138 may effectively experience little to no strain duringcrimping. The longitudinally extending strut 138 may be one single strutextending through both rows of cells 134 a/134 b. Further, as shown eachcell of the rows of cells 134 a/134 b can be circumferentially betweenlongitudinally extending struts 138.

As shown in the illustrated embodiment, the upper row of cells 134 a andthe lower row of cells 134 b extend in a direction generally parallel tothe longitudinal axis of the prosthesis 100. There can be a row ofeighteen cells 134 a and a row of eighteen cells 134 b. While each ofthe cells 134 a-b are shown as having the same shape as other cells 134a-b of the same row but mirrored, it is to be understood that the shapesof cells 134 a-b within a row can differ. Moreover, it is to beunderstood that any number of rows of cells can be used and any numberof cells may be contained in the rows. In some embodiments, the numberof cells can correspond to the number of anchors or anchor tips formingthe inner frame anchoring feature 124. In some embodiments, both rows ofcells 134 a-b can have different numbers of cells. Moreover, it is to beunderstood that fewer or greater numbers of rows of cells can be used.

The geometry of cells 134 a-b can allow the cells 134 a-b to foreshortenas the inner frame 120 is expanded. As such, one or more of cells 134a-b can allow the inner frame 120 to foreshorten as the inner frame 120is expanded. Foreshortening of the inner frame 120 can be used to securethe prosthesis to intralumenal tissue in a body cavity such as tissue ator adjacent a native valve including, but not limited to, a native valveannulus and/or leaflets. For example, expansion of the inner frame 120can allow the inner frame anchoring feature 124 to extend radiallyoutward and draw closer to tissue of the body cavity, such as a nativevalve annulus and/or leaflets, to engage tissue of the body cavity. Insome embodiments, the use of longitudinally extending strut 138 canreduce the foreshortening.

Additionally, as shown in FIG. 2, the inner frame 120 can include tabs(or locking tabs) 104 extending from a portion of the inner frame 120.The tabs 104 can extend at or proximate an upper end of the upper region126 of the inner frame body 122 such as upper apices of cells 134 a. Theinner frame 120 can include twelve locking tabs 104, however, it is tobe understood that a greater number or lesser number of locking tabs canbe used, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11. The locking tabs104 can extend generally upwardly from the upper region 126 of the innerframe body 122 in a direction generally aligned with the longitudinalaxis of the prosthesis 100. As shown in the illustrated embodiment, thelocking tabs 104 can include a longitudinally-extending strut 132 a. Atan upper end of the strut 132 a, the locking tab 104 can include anenlarged head 132 b. As shown, the enlarged head 132 b can have asemi-circular or semi-elliptical shape forming a “mushroom” shape withthe strut 132 a.

In some embodiments, the inner frame 120 can include an eyelet 106. Theeyelet 106 can be advantageously used to couple the inner frame 120 toan outer frame 140. For example, a suture can be passed through theeyelet 106 for coupling to an eyelet 143 of the outer frame 140. In someembodiments, the eyelet 106 can be used to couple to other components ofa prosthesis in which the inner frame 120 is used such as, but notlimited to, a valve body and/or a skirt.

While the locking tabs 104 have been described as being attached to theinner frame body 122, it is to be understood that the locking tabs 104can be attached to other portions of the prosthesis 100 such as, but notlimited to, the outer frame body 142. For example, in some embodiments,the locking tabs 104 can extend from an upper end of an upper region 146of the outer frame body 142. Moreover, it is to be understood thatportions of, or the entirety of, the locking tabs 104 can be omitted.For example, in some embodiments, the strut 132 a can be omitted suchthat the enlarged head 132 b and eyelet 106 are positioned at an upperend of the upper region 126 of the inner frame body 122, such as atupper apices of cell 134 a.

In some embodiments, each tab 104 can be aligned vertically over aninner frame anchoring feature 124. In some embodiments, each tab 104 iscircumferentially offset from an inner frame anchoring feature 124. Insome embodiments, there are the same number of tabs 104 as inner frameanchoring features 124. In some embodiments, there are a differentnumber of tabs 104 as inner frame anchoring features 124. There can bemore tabs 104 than inner frame anchoring features 124. There can be lesstabs 104 as inner frame anchoring features 124.

In some embodiments, the tab 104 can be advantageously used to couplethe inner frame 120 with multiple types of delivery systems. Forexample, the shape of the tab 104 can be used to secure the inner frame120 to a “slot” based delivery system. The eyelets 106 can be used tosecure the inner frame 120 to a “tether” based delivery system such asthose which utilize sutures, wires, or fingers to control delivery ofthe inner frame 120 and the prosthesis. This can advantageouslyfacilitate recapture and repositioning of the inner frame 120 and theprosthesis in situ. In some embodiments, the inner frame 120 andprosthesis can be used with the delivery systems described herein,including but not limited to, those described in U.S. Pat. Nos.8,414,644 and 8,652,203 U.S. Publication Nos. 2015/0238315,2019/0008640, 2017/0056169, 2016/0317301 and 2017/0056171, theentireties of each of which have been incorporated by reference herein.In such embodiments, the tab 104 may be omitted to advantageously theaxial dimension between the upper end and the lower end of the innerframe 120 (i.e., the “height” of the inner frame 120).

The inner frame 120, and any other frame described herein, may includefeatures and concepts similar to those disclosed in U.S. Pat. Nos.8,403,983, 8,414,644, and 8,652,203, U.S. Publication Nos. 2011/0313515,2014/0277390, 2014/0277427, 2014/0277422, 2015/0328000, 2018/0021129,and 2018/0055629, the entireties of each of which are herebyincorporated by reference and made a part of this specification. This isinclusive of the entire disclosure and is not in any way limited to thedisclosure of the associated frames. Moreover, although the inner frame120 has been described as including an inner frame body 122 and an innerframe anchoring feature 124, it is to be understood that the inner frame120 need not include all components. For example, in some embodiments,the inner frame 120 can include the inner frame body 122 while omittingthe inner frame anchoring feature 124. Moreover, although the innerframe body 122 and the inner frame anchoring feature 124 have beenillustrated as being unitarily or monolithically formed, it is to beunderstood that in some embodiments the inner frame body 122 and theinner frame anchoring feature 124 can be formed separately. In suchembodiments, the separate components can be attached using any of thefasteners and/or techniques described herein. For example, the innerframe anchoring feature 124 can be formed separately from the innerframe body 122 and can be attached to the inner frame body 122.

FIGS. 5A-5E illustrates an inner frame 220 with an “hourglass” orgenerally hourglass shape. A full multi-portion replacement valve withan hourglass inner frame is shown with respect to FIGS. 30A-30D. Theinner frame 220 can incorporate any or all of the features discussedabove with respect to inner frame 120, for example inner frame anchoringfeature 124, and the inner frame 120 can incorporate any or all of thefeatures discussed above with respect to inner frame 220. Inner frame220 can include an upper region 226, an intermediate region 228, and alower region 230. As shown, the intermediate region 228 can have asmaller diameter than the upper region 226, the lower region 230, orboth. This can form an hourglass shape wherein the intermediate region228 is thinner in diameter than both the upper region 226 and the lowerregion 230. In some embodiments, the upper region 226 and the lowerregion 230 can have approximately the same diameter. In someembodiments, the upper region 226 can have a larger diameter than thelower region 230. In some embodiments, the upper region 226 can have asmaller diameter than the lower region 230.

FIGS. 5A-5E further illustrates that the inner frame 220 can smoothlytransition between the different diameters forming a curved shape. Insome embodiments, the struts making up the inner frame 220 can be curvedto form the hourglass. In some embodiments, the struts can be relativelystraight, and there can be inflection points in the struts or at meetingpoints between the struts. In some embodiments, the inner frame 220 canbe concave. In some embodiments, a portion of the inner frame 220, suchas the upper region 226, the intermediate region 228, and/or the lowerregion 230 may be concave. In some embodiments, the inner frame 220 cancurve inward, or be thinner, in the middle than at the top and bottom.In some embodiments, the inner frame 220 can form the hourglass shape inits fully expanded form. In some embodiments, an hourglass can be shapedfrom a linear radially inwards taper from the upper region 226 to theintermediate region 228 (so the diameter is smaller at the intermediateregion 228 than the upper region 226) and a subsequent radially outwardstaper (e.g., reversing the taper) from the intermediate region 228 tothe lower region 230 (so the diameter is smaller at the intermediateregion 228 than the lower region 230). In some embodiments, the frame220 may have a tapered waist or a narrowed waist.

In some embodiments, the inner frame 220 can taper radially inwards(e.g., reducing diameter) in one direction from one end to the otherend. For example, the upper region 226 may have the largest diameter,and the inner frame 220 can taper radially inwards to the intermediateregion 228, and further radially inwards to the lower region 230. Insome embodiments, the lower region 230 may have the largest diameter,and the inner frame 220 can radially inwards to the intermediate region228, and further radially inwards to the upper region 226. The taper maybe smooth, or may be a series of straight portions, like steps. In someembodiments, the taper may occur in 1, 2, 3, 4, 5 straight linesreducing the diameter. In some embodiments, the taper may be curved. Insome embodiments, the taper may be linear.

In some embodiments, a portion of the inner frame 220 may be taperedradially inwards, and a different portion may be cylindrical (orgenerally cylindrical). For example, the upper region 226 may be taperedradially inwards, but the intermediate region 228 and/or the lowerregion 230 may be cylindrical. In some embodiments, the lower region 230may be tapered radially inwards, but the intermediate region 228 and/orthe upper region 226 may be cylindrical.

In some embodiments, a portion of the inner frame 220 may be taperedradially inwards, and a different portion may be concave (or generallyconcave). For example, the upper region 226 may be tapered radiallyinwards, but the intermediate region 228 and/or the lower region 230 maybe generally. In some embodiments, the lower region 230 may be taperedradially inwards, but the intermediate region 228 and/or the upperregion 226 may be generally.

The hourglass shape and/or tapering described above can allow for theleaflets of the valve to be “flush” against the inner frame 220 whenopened. Further, the longitudinal length of the leaflets can be againstthe inner frame 220 as much as possible. For example, each of the valveleaflets can have an inlet end positioned along the decreasing diameterportion of the frame as discussed above. Additionally, the narrowerintermediate region 228 can provide for smaller replacement valveleaflets to be used, and the smaller diameter can allow for increasedblood flow through the narrower area.

Embodiments of the inner frame 220 can advantageously reducethrombogenicity. For example the hourglass shape can help create avortex which encourages particles to be washed-out during valve openingwith high turbulence during closing. This can also include squeezing outany thrombus that may be forming in the gap between leaflets and theframe 220. In addition, this shape can reduce leaflet thickening, whichcan cause increased risk of stroke. This can allow for the reduction oravoidance of blood thinners, or at least the avoidance of lifetime bloodthinners. This could clinically lead to less anticoagulation, betterdurability, and lower stroke.

FIGS. 5F-5I illustrate the valve leaflets 231 opening in an hourglassshaped frame 220. FIG. 5F shows the outflow end open, FIG. 5G shows theinflow end open, FIG. 5H shows the outflow end closed, and FIG. 5I showsthe inflow end closed. In some embodiments, the inlet end of the valveleaflets 231 can lie flat along the inner frame 220 when the valve isopen. Thus, if the inner frame 220 is in a cylindrical frame, the valveleaflets 231 may not be parallel to the walls of the frame because theleaflets 231 naturally are inclined outwards in the opened position,causing compression or distortion of the leaflets. However, using theinner frame 220 shapes described above (an hourglass, tapered, concaveor similar shape) where the valve leaflet 231 inlets are, then the valveleaflets 231 more naturally rest closer to the frame 220 itself when thevalve is open as shown in FIGS. 5F and 5G, and do not compress ordeform. Thus, the leaflets 231 follow the shape of the hourglass frame220 when opening, providing for optimal washout. In some embodiments,the leaflets 231 can be attached generally at the intermediate region228, so when the leaflets 231 are opened they can extend furtherradially outwards in the larger diameter regions.

Further, the hourglass inner frame 220 can allow for the leaflets of thevalve body to conform with and/or contact the inner surface of thehourglass inner frame 220. Thus, the hourglass design can improvewashout by reducing any gap between the seamline of the leaflets and thewall of the inner frame 220 on which the leaflets are attached to.Specifically, FIG. 5J shows the leaflets 262 in the closed position andFIG. 5K shows the leaflets 262 in the fully open position generallyconforming to the inner frame 220. Thus, as shown, in some embodimentsthe only portions of each of the leaflets 262 that do not contact theframe 220 when opened are the free edges of the leaflets 262 at theoutlet end. Accordingly, almost the entire “belly” or “surface” of eachof the leaflets 262 (e.g., the surface of the leaflets 262 which facethe interior surface of the inner frame 220) conform to and/or contactthe inner frame 220 of the hourglass shape (e.g., reducing any gapbetween the leaflets 262 and the interior surface of the inner frame220). In some embodiments, over 50%, over 75%, over 90%, over 95%, orover 99% of the belly of the leaflets 262 can conform to and contact theinterior surface of the inner frame 220 when in the fully open position.In some embodiments, the free edges of the outlet end of the leaflets262 do not contact the inner frame 220. In some embodiments, only thefree edges of the outlet end of the leaflets 262 do not contact theinner frame 220. In some embodiments, the free edges of the outlet endof the leaflets 262 are spaced away from the interior surface of theinner frame 220.

This configuration can be advantageous as free edges contacting theframe can create major durability issues, as constant opening andclosing can wear on the edges and damage/destroy them. Thus,advantageously the hourglass inner frame 220 is shaped to achieveoptimal contact between the leaflet surface and the frame surface whenthe leaflets 262 are fully opened while avoiding contact by the freeedges to reduce overall damage to the leaflets during motion. This canimprove washout and reduce thrombogenicity, while also providing a moredurable leaflet.

While the hourglass and tapering shape is described above in conjunctionwith the inner frame 220, similar dimensions/shapes can be used withrespect to the outer frame 140 or a single frame prosthesis. Further,this can be applied to any type of valve, such as a replacement mitralvalve or a replacement aortic valve.

FIG. 31 illustrates an example alternate configuration of the hourglassshape discussed above for the inner frame 220, and can include any orall of the features discussed with respect to frames 120/220 shown inFIGS. 2 and 5A. Instead of the inner frame 220′ being an hourglass shapeas discussed above with respect to inner frame 220, the inner frame 220′can have a non-hourglass cylindrical shape such as shown in FIG. 2between its upper region 226′, intermediate region 228′, and lowerregion 230′, as shown in FIG. 31. For example, the inner frame 220′ canhave a substantially constant cross-sectional dimension, e.g., generallycircular, between its upper region 226′, intermediate region 228′, andlower region 230′. An additional secondary inner frame 502 can then beattached (permanently or removably) on an inner surface of the innerframe 220′. The secondary inner frame 502 can have a generally circularcross section.

The secondary inner frame 502 can be shaped to form an hourglass withinthe lumen of the inner frame 220′. For example, an intermediate region288′ can have a smaller radial diameter than the upper region 226′ andthe lower region 230′. In some embodiments, the upper region 226′ andthe lower region 230′ can have approximately the same dimensions. Inother embodiments, the dimensions may be different. In some embodiments,the transition between different diameters can be smooth, such as with acurve, or can be angular with discrete corners. The secondary innerframe 502 can have a concave shape.

As shown in FIG. 31, the secondary inner frame 502 can attach generallyat proximal (e.g., in the upper region 226′) and distal (e.g., in thelower region 230′) ends of the secondary inner frame 502, and a centralportion of the secondary inner frame 502 can be located radially inwardsfrom the ends and from the inner surface of the inner frame 220′.

In some embodiments, a proximal portion of the secondary inner frame 502can be attached to the inner frame 220′ proximal to where the tabs 104begin. In some embodiments, a proximal portion of the secondary innerframe 502 can be attached to the inner frame 220′ distal to where thetabs 104 begin. In some embodiments, a proximal portion of the secondaryinner frame 502 can be attached to the inner frame 220′ where the tabs104 begin.

In some embodiments, a distal portion of the secondary inner frame 502can be attached to the inner frame 220′ proximal to where the innerframe anchoring feature 124 begins bending radially outwards. In someembodiments, a distal portion of the secondary inner frame 502 can beattached to the inner frame 220′ distal to where the inner frameanchoring feature 124 begins bending radially outwards. In someembodiments, a distal portion of the secondary inner frame 502 can beattached to the inner frame 220′ where the inner frame anchoring feature124 begins bending radially outwards.

The secondary inner frame 502 can be attached to the inner frame 220′by, for example, sutures, adhesives, frictional forces, mechanicalattachment, or the two frames can be integrally formed together.

The secondary inner frame 502 can be an “ultra-thin walled” inner frame,such as between 200-400 microns of thickness, though the particular sizeis not limiting. For example, the secondary inner frame 502 may beformed of a plurality of longitudinal strips (e.g., ribs), for examplemetallic, composite, or polymer strips. The strips could bow inwardly asthe inner frame 220′ foreshortens upon radial expansion. In someembodiments, the strips could always be bowed inwardly. In someembodiments, the strips could be used in combination with a fabric orpolymer. Thus, the secondary inner frame 502 could generally be a tubeof fabric with a plurality of ribs on the outside of the fabric thatwould push the fabric inwardly to form the hourglass shape.Alternatively, a thin braided mesh which can bow inwardly, such asduring foreshortening, could be used in conjunction with a fabric asdiscussed above.

In some embodiments, a cloth or other fabric can be used to form thehourglass shape. For example, the cloth could act as a pocket that wouldfill with blood and harden over time into the particular hourglassshape. Alternatively, a balloon could be used to form the hourglassshape where the balloon could be filed with saline or otherbiocompatible fluid.

In some embodiments, a swellable material could be used to form thesecondary inner frame 502. The swellable material could absorb water, orother fluid, from blood and swell into the desired shape.

The secondary inner frame 502 can be advantageous as it leverages thehighly stable cylindrical inner frame design of inner frame 220′ whilestill providing the anti-thrombosis benefit of the hourglass secondaryinner frame 502.

Outer Frame

With reference next to the outer frame 140 which is illustrated alone inFIGS. 6A-6D. The outer frame 140 can be incorporated into a prosthesiswith any of the variations of the described inner frames. The outerframe 140 can provide a structure to which various components of theprosthesis 100 can be attached. The outer frame 140 can be attached tothe inner frame 120 using any of the fasteners and/or techniquesdescribed herein including, but not limited to, mechanical fasteners,such as sutures, staples, fabric screws, rivets, interfacing members(e.g., tabs and slots which can be on the inner frame 120 and the outerframe 140), and any other type of mechanical fastener as desired,chemical fasteners such as adhesives and any other type of chemicalfastener as desired, fastening techniques such as welding, soldering,sintering, and any other type of fastening technique as desired, and/ora combination of such fasteners and techniques. In some embodiments, theinner frame 120 and the outer frame 140 can be indirectly attached viaan intermediate component, such as the skirt 180. In some embodiments,sutures are used to attached eyelet 143 of the outer frame 140 witheyelet 106 of the inner frame 120.

The outer frame 140 can be attached to the inner frame 120 at one ormore attachment points. The outer frame 140 can be tautly attached tothe inner frame 120 such that little to no relative movement between theouter frame 140 and the inner frame 120 occurs at the one or moreattachment points. In other embodiments, the outer frame 140 can beloosely attached to the inner frame 120 such that some relative movementbetween the outer frame 140 and the inner frame 120 can occur at the oneor more attachment points. Although the outer frame 140 is illustratedas a separate component from the inner frame 120, it is to be understoodthat the frames 120, 140 can be unitarily or monolithically formed.

As shown in the illustrated embodiment, the outer frame 140 can includean outer frame body 142. In some embodiments, such as shown in FIG. 12,the outer frame 140 can further include an outer frame anchoring feature144 (if used in a mitral valve, also known as an atrial or proximalanchor). However, as shown in FIGS. 6A-6D (and FIGS. 9-11), the outerframe may not include an outer frame anchoring feature 144.

The outer frame body 142 can have an upper region 146, an intermediateregion 148, and a lower region 150. In some situations, such as those inwhich the prosthesis 100 is positioned within a native mitral valve, theupper region 146 can be generally positioned supra-annularly, theintermediate region 148 can be generally positioned intra-annularly, andthe lower region 150 can be positioned sub-annularly. However, it is tobe understood that in some situations, the positioning of the outerframe 140 relative to the annulus can differ. Moreover, it is to beunderstood that in some embodiments, the outer frame 140 can omit one ormore of the upper region 146, the intermediate region 148, and/or thelower region 150.

When in an expanded configuration such as a fully expandedconfiguration, the outer frame body 142 can have an enlarged/bulbousshape with the intermediate region 148 and the lower region 150 beinglarger than the upper region 146, or the intermediate region 148 beinglarger than the lower region 150 and the upper region 146. The bulbousshape of the outer frame body 142 can advantageously allow the outerframe body 142 to engage a native valve annulus, native valve leaflets,or other body cavity, while spacing the inlet and outlet from the heartor vessel wall. This can help reduce undesired contact between theprosthesis 100 and the heart or vessel, such as the atrial andventricular walls of the heart. The bulbous shape can further enhancesecurement of the outer frame body 142 to the body cavity. For example,in some embodiments, the bulbous shape can allow the intermediate region148 to extend further radially outward compared to an anchoring feature.In this manner, the intermediate region 148 can exert a greater radialforce on tissue of the body cavity and/or can more completely conform tothe tissue of the body cavity, such as the native valve annulus and/ornative leaflets.

The upper region 146 of the outer frame body 142 can include a generallylongitudinally-extending section 146 a and an outwardly-extendingsection 146 b. The longitudinally-extending section 146 a can begenerally concentric with the inner frame body 122. Theoutwardly-extending section 146 b can extend radially outwardly awayfrom the longitudinal axis 102 of the prosthesis 100. Theoutwardly-extending section 146 b can extend in a direction that is moreperpendicular to the longitudinal axis 102 than parallel and/or in adownward direction from the longitudinally-extending section 146 a.However, it is to be understood that the outwardly-extending section 146b can extend generally perpendicularly to the longitudinal axis 102and/or in an upward direction from the longitudinally-extending section146 a. Moreover, it is to be understood that thelongitudinally-extending section 146 a can be omitted such that theupper region 146 extends radially outwardly at the upper end of theupper region 146.

At the juncture between the longitudinally-extending section 146 a andthe outwardly-extending section 146 b, the outer frame body 140 caninclude a bend 152. The bend 152 can be about a circumferential axissuch that the outwardly-extending section 146 b extends in a directionmore perpendicular to the longitudinal axis of the outer frame 140 thanthe longitudinally-extending section 146 a. In some embodiments, thebend 152 can generally form an arc with an angle between about 20degrees to about 90 degrees. For example, as shown in the illustratedembodiment, the arc can have an angle of about 60 degrees. In someembodiments, the bend 152 can form an arc with an angle between about 30degrees to about 60 degrees. The radius of curvature of the arc may beconstant such that the bend 152 forms a circular arc or may differ alongthe length of the bend 152.

In some embodiments, the outwardly-extending section 146 b can form anangle of between about 20 degrees to about 70 degrees with a planeorthogonal to the longitudinal axis of the prosthesis 100, an angle ofbetween about 30 degrees to about 60 degrees with a plane orthogonal tothe longitudinal axis of the prosthesis 100, an angle of between about40 degrees to about 50 degrees with a plane orthogonal to thelongitudinal axis of the prosthesis 100, an angle of about 45 degreeswith a plane orthogonal to the longitudinal axis of the prosthesis 100,any subrange within these ranges, or any other angle as desired. In someembodiments, the outwardly-extending section 146 b can form an angle ofless than 70 degrees with a plane orthogonal to the longitudinal axis ofthe prosthesis 100, an angle of less than 55 degrees with a planeorthogonal to the longitudinal axis of the prosthesis 100, an angle ofless than 40 degrees with a plane orthogonal to the longitudinal axis ofthe prosthesis 100, an angle of less than 25 degrees with a planeorthogonal to the longitudinal axis of the prosthesis 100, or less thanany other angle as desired.

The intermediate region 148 of the outer frame body 142 can extendgenerally downwardly from the outwardly-extending section 146 b of theupper region 146. As shown, the intermediate region 148 can have agenerally constant diameter from an upper end of the intermediate region148 to a lower end of the intermediate region 148 such that theintermediate region 148 forms a generally cylindrical shape. However, itis to be understood that the diameters of the upper end, the lower end,and/or the portion therebetween can be different. For example, adiameter of the portion between the upper end and the lower end can belarger than the upper end and the lower end such that the intermediateregion 148 has a generally bulbous shape. In some embodiments, thediameter of the lower end can be larger than the diameter of the upperend. In other embodiments, the diameter of the upper end can be largerthan the diameter of the lower end. Moreover, although the outer framebody 142 has been described and illustrated as being cylindrical orhaving circular cross-sections, it is to be understood that all or aportion of the outer frame body 142 can be have a non-circularcross-section such as, but not limited to, a D-shape, an oval or anotherwise ovoid cross-sectional shape.

In some embodiments, the lower region 150 can be curved and/or inclinedtowards the longitudinal axis of the frame such that the lower ends ofthe lower region 150 can extend in a direction that is between about 20degrees to about 80 degrees with respect to a plane parallel to thelongitudinal axis, between about 25 degrees to about 70 degrees withrespect to a plane parallel to the longitudinal axis between about 30degrees to about 60 degrees with respect to a plane parallel to thelongitudinal axis, about 30 degrees with respect to a plane parallel tothe longitudinal axis. The lower region 150 can be curved and/orinclined towards the longitudinal axis such that the lower ends of thelower region 150 can extend in a direction generally perpendicular tothe longitudinal axis.

In some embodiments, the outer frame body 142 in an expandedconfiguration can have a diameter at its widest portion of between about30 mm to about 60 mm, between about 35 mm to about 55 mm, about 40 mm,any sub-range within these ranges, or any other diameter as desired. Insome embodiments, the outer frame body 142 in an expanded configurationcan have a diameter at its narrowest portion between about 20 mm toabout 40 mm, any sub-range within these ranges, or any other diameter asdesired. In some embodiments, the outer frame body 142 in an expandedconfiguration can have a diameter at a lower end of the lower region 150between about 20 mm to about 40 mm, any sub-range within these ranges,or any other diameter as desired. In some embodiments, in an expandedconfiguration, the ratio of the diameter of the outer frame body 142 atits widest portion to the diameter of the frame body 142 at itsnarrowest portion can be about 3:1, about 5:2, about 2:1, about 3:2,about 4:3, any ratio within these ratios, or any other ratio as desired.

The outer frame body 142 can have an axially compact configurationrelative to the radial dimension. The outer frame body 142 in anexpanded configuration can have an the axial dimension between the upperand lower ends of the outer frame body 142 (i.e., the “height” of theouter frame body 142) of between about 10 mm to about 40 mm, betweenabout 18 mm to about 30 mm, about 20 mm, any sub-range within theseranges, or any other height as desired. In some embodiments, the ratioof the diameter of the largest portion of the outer frame body 142 tothe height of the outer frame body 142 when the frame is in its expandedconfiguration can be about 3:1, about 5:2, about 2:1, about 3:2, about4:3, about 13:10, about 5:4, or about 1:1. Thus, in some embodiments thewidth at the largest portion of the outer frame body 142 can be greaterthan the height of the outer frame body 142.

With continued reference to the outer frame 140 illustrated in FIGS.6A-6D, the outer frame body 142 can include a plurality of struts withat least some of the struts forming cells 154. Any number ofconfigurations of struts can be used, such as rings of undulating strutsshown forming ellipses, ovals, rounded polygons, and teardrops, but alsochevrons, diamonds, curves, and various other shapes.

The cells 154 can have an irregular octagonal shape such as a “teardrop”shape. The cells 154 can be formed via a combination of struts. As shownin the illustrated embodiment, the upper portion of cells 154 can beformed from a set of circumferentially-expansible struts 156 a having azig-zag or undulating shape forming a repeating “V” shape. Thecircumferentially-expansible struts 156 a can be inclined or curvedradially outwardly away from the longitudinal axis of the prosthesis 100such that an upper portion of the struts 156 a are positioned closer tothe longitudinal axis of the prosthesis 100 than the lower portion ofthe struts 156 a. The bottom portion of cells 154 can be formed from aset of struts 156 b extending downwardly from a central or generallycentral location of each of the “V” shapes. The struts 156 b can extendalong with a plane parallel to and/or extending through the longitudinalaxis of the prosthesis 100.

While the struts 156 are generally described and illustrated as beingstraight segments, it is to be understood that some or all of the struts156 may not form entirely straight segments. For example, the struts 156can include some curvature such that the upper and/or lower apices arecurved.

The geometry of cells 154 can allow the cells 154 to foreshorten as theouter frame 140 is expanded. As such, one or more of cells 154 can allowthe outer frame 140 to foreshorten as the outer frame 140 is expanded.Foreshortening of the outer frame 140 can be used to secure theprosthesis to intralumenal tissue in a body cavity such as tissue at oradjacent a native valve including, but not limited to, a native valveannulus and/or leaflets. For example, expansion of the outer frame 140can allow the outer frame 140 to exert a radially outward force againstthe tissue at or adjacent the native valve, such as the native valveannulus and/or leaflets.

FIGS. 7A-7B illustrate a flat pattern of the outer frame 140 in thecompressed (FIG. 7A) and expanded (FIG. 7B) position. As shown, struts156 b are generally held circumferentially between struts 156 a in boththe compressed and expanded position. Further, in some embodiments, thestruts 156 a/156 b can be asymmetric, thus making some strutscompressible/expandably weaker than other struts. In particularly,struts 156 b can have a different width/thickness than struts 156 a.While symmetric cells can have uneven expansion and crimp, theasymmetric cells disclosed herein can have even expansion and crimping.Further, having the different width/thickness can promote stability ofthe valve. The larger struts can be what the delivery system hold onto,so these can be stronger so when the delivery system crimps theprosthesis 100, it has more leverage over the thinner struts. However,in some embodiments struts 156 a/156 b are the same thickness/width(e.g., are symmetric).

In some embodiments, struts 156 b can be 100%, 95%, 90%, 80%, 70%, 60%,50%, 40%, or 30% the thickness/width of struts 156 a. In someembodiments, struts 156 b can be less than 100%, 95%, 90%, 80%, 70%,60%, 50%, 40%, or 30% the thickness/width of struts 156 a. In someembodiments, struts 156 b can be greater than 95%, 90%, 80%, 70%, 60%,50%, 40%, or 30% the thickness/width of struts 156 a.

FIGS. 7C-7D illustrates another embodiment of a flat pattern of an outerframe 140, and can include any or all of the features discussed abovewith respect to FIGS. 7A-7B. Features disclosed with respect to FIGS.7C-7D can be used in conjunction with, or instead of any of the outerframe features discussed herein. Advantageously, the outer frame 140 caninclude a notch 151 that partially extends into the strut 156 a′ at theconnection between the struts 156 a′/156 b′. The notch can be rounded,as shown in FIG. 7D, or may be triangular, squared, or another cutpattern and the particular shape of the notch is not limiting. The notch151 can save approximately 0.25 mm of material per strut, allowing for atotal reduction of 4.55 mm in circumference as compared to non-notchedconfigurations. Further, as the peak force is generally at theconnection of the struts 156 a′/156 b′, and the design can reduce theoverall straight on the outer frame 140.

Additionally, the outer frame 140 can include a tab 145 extendingproximally away from the eyelet 143, such as also shown in the followingFIGS. 8A-8B. This can allow for better attachment between the outerframe and the inner frame, for example by allowing for a second apertureper strut and more area for sutures to attach, and can provide for analternative attachment mechanism. Thus, the tab 145 can be, for example,a mushroom tab as disclosed herein with respect to the inner frame 120,and may allow for attachment into the delivery system.

FIGS. 8A-8B illustrate flat patterns of alternative configurations ofthe outer frame 140, and can include any or all of the featuresdisclosed above with respect to FIGS. 7A-7D. Notably, FIG. 8Aillustrates an outer frame 140 having outer frame anchoring feature 144,an expanded version of which is shown in FIG. 12. In addition, bothFIGS. 8A and 8B include tabs 145 extending upwards.

In embodiments including the outer frame anchoring feature 144, such asshown in FIG. 12, the outer frame anchoring feature 144 can extendoutwardly relative to the longitudinal axis 102 of the prosthesis 100.The outer frame anchoring feature 144 can extend at or proximate thejuncture between the upper region 146 and the intermediate region 148 ofthe outer frame body 142. The outer frame anchoring feature 144 canextend in a direction that is more perpendicular to the longitudinalaxis 102 than parallel and/or can extend in a downward direction fromthe longitudinally-extending section 146 a. The outer frame anchoringfeature 144 can extend in a direction generally aligned with theoutwardly-extending section 146 b of the upper region 146. However, itis to be understood that the outer frame anchoring feature 144 canextend generally perpendicularly to the longitudinal axis 102 and/or inan upward direction.

In some embodiments, the outer frame anchoring feature 144 can extend ina direction that is more perpendicular to the longitudinal axis of theprosthesis 100 than parallel. As shown, the outer frame anchoringfeature 144 can extend in a downward direction generally parallel to theoutwardly-extending section 146 b. In some embodiments, the outer frameanchoring feature 144 can extend generally perpendicularly to thelongitudinal axis 102 and/or in an upward direction.

As shown in the illustrated embodiment, the outer frame 140 can includetabs 118 extending from a portion of the outer frame 140 such as anupper end of the outer frame 140. The tabs 118 can include an eyelet143. The tab 118 can be advantageously used to couple the outer frame140 to an inner frame 120 of the prosthesis. For example, a suture canbe passed through the eyelet 143 for coupling to an inner frame 120. Insome embodiments, the tabs 118 can be used to couple to other componentsof a prosthesis in which the outer frame 140 is used such as, but notlimited to, a valve body and/or a skirt.

In some embodiments, the tab 118 can be advantageously used to couplethe outer frame 140 with multiple types of delivery systems. Forexample, the shape of the tab 118 can be used to secure the outer frame140 to a “slot” based delivery system. The eyelets 120 can be used tosecure the outer frame 140 to a “tether” based delivery system such asthose which utilize sutures, wires, or fingers to control delivery ofthe outer frame 140 and the prosthesis. This can advantageouslyfacilitate recapture and repositioning of the outer frame 140 and theprosthesis in situ. In some embodiments, the outer frame 140 andprosthesis can be used with the delivery systems described herein,including but not limited to, those described in U.S. Pat. Nos.8,414,644 and 8,652,203 and U.S. Publication Nos. 2015/0238315, theentireties of each of which are incorporated by reference herein. Insome embodiments, a tab can be positioned at an end of a strut similarto locking tabs 232.

While the below discusses anchoring features 124, 144, it will beunderstood that the prosthesis 100 may not include feature 144. One orboth anchoring features 124, 144 (if used) can contact or engage anative valve annulus, such as the native mitral valve annulus, tissuebeyond the native valve annulus, native leaflets, and/or other tissue ator around the implantation location during one or more phases of thecardiac cycle, such as systole and/or diastole. In some embodiments, oneor both anchoring features 124, 144 (if used) do not contact or engage,or only partially contact or engage, a native valve annulus, such as thenative mitral valve annulus, tissue beyond the native valve annulus,native leaflets, and/or other tissue at or around the implantationlocation during one or more phases of the cardiac cycle, such as systoleand/or diastole. However, it is to be understood that in someembodiments, when the prosthesis 100 is used for a replacement mitralvalve prosthesis, during diastole and/or systole, both the inner frameanchoring feature 124 and the outer frame anchoring feature 144 (ifused) can be sized to contact or engage the native mitral valve annulus.

The anchoring features 124, 144 (if used) and anchor tips 124 a, 144 a(if used) are preferably located along the prosthesis 100 with at leastpart of the foreshortening portion positioned between the anchoringfeatures 124, 144 (if used) so that a portion of the anchoring features124, 144 (if used) will move closer together with expansion of theprosthesis 100. This can allow the anchoring features 124, 144 (if used)to close in on opposite sides of the native mitral annulus to therebysecure the prosthesis at the mitral valve. In some embodiments, theanchoring features 124, 144 (if used) can be positioned such that theanchoring features 124, 144 (if used) do not contact opposing portionsof the native mitral annulus at the same time. For example, when theprosthesis 100 is used for a replacement mitral valve prosthesis, duringat least systole, in some embodiments the inner frame anchoring feature124 is sized to contact or engage the native mitral valve annuluswhereas the outer frame anchoring feature 144 (if used) is sized to bespaced from the native mitral valve annulus. This can be beneficial whenouter frame anchoring feature 144 (if used) is used to providestabilization and help align the prosthesis. In some embodiments, theanchoring features 124, 144 (if used) can be positioned such that theanchoring features 124, 144 (if used) grasp opposite side of the nativemitral annulus.

While the anchoring features 124, 144 (if used) have been illustrated asextending from the lower end of the lower region 130 of the inner framebody 122 and at a junction between the upper region 146 and theintermediate region 148 of the outer frame body 142 respectively, it isto be understood that the anchoring features 124, 144 (if used) can bepositioned along any other portion of the prosthesis 100 as desired.Moreover, while two anchoring features 124, 144 (if used) have beenincluded in the illustrated embodiment, it is to be understood that agreater number or lesser number of sets of anchoring features can beutilized.

Components of the outer frame 140, such as the outer frame body 142 canbe used to attach or secure the prosthesis 100 to a native valve, suchas a native mitral valve. For example, the intermediate region 148 ofthe outer frame body 142 and/or the outer anchoring feature 144 can bepositioned to contact or engage a native valve annulus, tissue beyondthe native valve annulus, native leaflets, and/or other tissue at oraround the implantation location during one or more phases of thecardiac cycle, such as systole and/or diastole. In situations where theouter frame body 142 is positioned within a native mitral valve, theouter frame body 142 can beneficially eliminate, inhibit, or limitdownwardly directed forces such as those which are applied on theprosthesis 100 during diastole and/or upwardly directed forces such asthose which are applied on the prosthesis 100 during systole. As anotherexample, the outer frame body 142 can be sized and positioned relativeto the inner frame anchoring feature 124 such that tissue of the bodycavity positioned between the outer frame body 142 and the inner frameanchoring feature 124, such as native valve leaflets and/or a nativevalve annulus, can be engaged or pinched to further secure theprosthesis 100 to the tissue. For example, the lower region 150 of theouter frame body 142 can be positioned at or proximate a tip or end ofthe inner frame anchoring feature 124. As shown, the lower region 150 ofthe outer frame body 142 is positioned such that at least a portion ispositioned radially inward of and below the inner frame anchoringfeature 124. In some embodiments, a portion of the outer frame 140, suchas the lower region 150, can be attached to the inner frame body 122 viaone or more tethers or sutures to limit the outward extension of theouter frame 140 relative to the inner frame body 122. This canbeneficially maintain a portion of the outer frame 140 between the innerframe body 122 and the inner frame anchoring feature 124. Although theinner frame anchoring feature 124 is shown extending from the innerframe body 122, it is to be understood that such an anchoring featurecan extend from the outer frame body 140.

Use of an inner frame 120 and an outer frame 140 can be beneficial forthe design of the prosthesis in that the inner frame 120 can be designedto suit the structure of the valve body 160 and the outer frame 140 canbe designed to suit the anatomy of the body cavity in which theprosthesis 100 is to be used. For example, the valve body 160 (shown inFIG. 10) can be cylindrical and have a smaller diameter than the bodycavity. In such an embodiment, the inner frame 120 can advantageouslyhave a smaller shape and/or size to support the valve body 160 while theouter frame 140 can have a larger shape and/or size to secure theprosthesis 100 to the body cavity. Moreover, in embodiments in which theouter frame 140 is larger than the inner frame 120, the shape of theouter frame 140 can beneficially enhance hemodynamic performance. Forexample, the shape of the outer frame 140 with a larger, generallycylindrical intermediate region 148 can allow for significant washout onan underside of the valve body 160. This washout can beneficially reducethe risk of thrombosis or clot formation under and around the valve body160.

The outer frame 140 can be formed from many different materialsincluding, but not limited to, a shape-memory metal such as Nitinol. Theouter frame 140 can be formed from a plurality of struts forming opencells. In some embodiments, the outer frame 140 can have a more flexibleconstruction as compared to other components of the prosthesis 100 suchas, but not limited to, the inner frame 120. This can be achieved, forexample, by the dimensions of the struts and by the configuration of thestruts. For example, fewer struts, thinner struts, and/or a differentmaterial for the struts can be used. The more flexible construction canallow the outer frame 140 to better conform to the anatomy of the bodycavity, such a native valve annulus and/or native leaflets. This can bebeneficial for anchoring against the body cavity and/or forming a sealagainst the body cavity. However, it is to be understood that in someembodiments the outer frame 140 can have a construction which is aboutas rigid as, or more rigid than, other components of the prosthesis 100,such as the inner frame 120.

The outer frame 140, and any other frame described herein, may includefeatures and concepts similar to those disclosed in U.S. Pat. Nos.8,403,983, 8,414,644, and 8,652,203, U.S. Publication Nos. 2011/0313515,2014/0277390, 2014/0277427, 2014/0277422, 2018/0021129, 2018/0055629,and 2015/0328000, the entireties of each of which have been incorporatedby reference. Moreover, although the outer frame 140 has been describedas including an outer frame body 142 and an outer frame anchoringfeature 144, it is to be understood that the outer frame 140 need notinclude all components. For example, in some embodiments, the outerframe 140 can include the outer frame body 142 while omitting the outerframe anchoring feature 144. Moreover, although the outer frame body 142and the outer frame anchoring feature 144 have been illustrated as beingunitarily or monolithically formed, it is to be understood that in someembodiments the outer frame body 142 and the outer frame anchoringfeature 144 can be formed separately. In such embodiments, the separatecomponents can be attached using any of the fasteners and techniquesdescribed herein. For example, the outer frame anchoring feature 144 canbe formed separately from the outer frame body 142 and can be attachedto the outer frame body 142.

Skirt

FIGS. 9-11 illustrate the prosthesis 100 with the skirt 180. The skirt180 can be attached to the inner frame 120 and/or outer frame 140 (orany of the alternate frames disclosed herein). As shown, the skirt 180can be positioned around and secured to a portion of, or the entiretyof, the exterior of the inner frame 120 and/or outer frame 140, such asin between the two frames 120/140. The skirt 180 can also be secured toa portion of the valve body 160. The skirt 180 can follow the contoursof the outer frame 140, such as the contours of the upper region 146,the intermediate region 148, and/or the lower region 150. In someembodiments, the skirt 180 can be used to attach the outer frame 140 tothe inner frame 120. Although not shown, it is to be understood that theskirt 180 can be positioned around and secured to a portion of, or theentirety of, an interior of the inner frame 120 and/or the outer frame140. Moreover, it is to be understood that while the skirt 180 canfollow the contours of portions of the inner frame 120 and the outerframe 140, at least a portion of the skirt 180 can be spaced apart fromat least a portion of both the inner frame 120 and the outer frame 140.In some embodiments, the skirt 180 can be spaced apart from the upperregion 146 of the outer frame 140. For example, the skirt 180 can bepositioned below the upper region 146. In such an embodiment, thespaced-apart portion of the skirt 180 can be loose such that the skirt180 is movable relative to the upper region 146 or can be taut such thatthe skirt 180 is generally fixed in position.

The skirt 180 can be annular and can extend entirely circumferentiallyaround the inner frame 120 and/or outer frame 140. The skirt 180 canprevent or inhibit backflow of fluids, such as blood, around theprosthesis 100. For example, with the skirt 180 positioned annularlyaround an exterior of the inner frame 120 and/or outer frame 140, theskirt 180 can create an axial barrier to fluid flow exterior to theinner frame 120 and/or outer frame 140 when deployed within a bodycavity such as a native valve annulus. The skirt 180 can encouragetissue in-growth between the skirt 180 and the natural tissue of thebody cavity. This may further help to prevent leakage of blood flowaround the prosthesis 100 and can provide further securement of theprosthesis 100 to the body cavity. In some embodiments, the skirt 180can be tautly attached to the inner frame 120 and/or outer frame 140such that the skirt 180 is generally not movable relative to the innerframe 120 and/or outer frame 140. In some embodiments, the skirt 180 canbe loosely attached to the inner frame 120 and/or outer frame 140 suchthat the skirt 180 is movable relative to the inner frame 120 and/orouter frame 140.

In some embodiments, the skirt 180 can be formed from a material such asknit polyester (e.g., polyethylene terephthalate (PET),polyvalerolactone (PVL)) or any other biocompatible material such asthose which are wholly or substantially fluid impermeable, flexible,stretchable, deformable, and/or resilient. The skirt 180 and/or theliner may be made from the same or similar materials. As shown in theillustrated embodiment, the skirt 180 can be formed as separatecomponents. The components can be attached together using any of thefasteners and/or techniques described herein including, but not limitedto, mechanical fasteners, such as sutures, staples, screws, rivets,interfacing members (e.g., tabs and slots), and any other type ofmechanical fastener as desired, chemical fasteners such as adhesives andany other type of chemical fastener as desired, fastening techniquessuch as welding, soldering, sintering, and any other type of fasteningtechnique as desired, and/or a combination of such fasteners andtechniques.

In some embodiments, the skirt 180 can be attached to the inner frame120, such as at one of the struts. For example, the skirt 180 can attachto longitudinally extending strut 138 or the circumferentially extendingstruts 136 a/13 b. The skirt 180 can be attached through sutures,adhesives, tying, etc. and the attachment is not limiting. In someembodiments, the skirt 180 can also be attached to the outer frame 140.

As the skirt 180 is attached to the inner frame 120, when the prosthesis100 first begins to crimp, such as for retraction/retrieval, the skirt180 is pulled inwardly with the inner frame 180. Thus, the skirt 180 canbe tucked between the struts of the outer frame 140. It can beadvantageous to perform this automatic tucking as in some embodiments alarge amount of material (such as cloth) of the outer skirt 180 isneeded to seal particularly large annuluses. Accordingly, the skirt 180can bunch up/prevent low profile crimping or require large amounts offorce to fully crimp the prosthesis because of the skirt 180 “clogging”the struts and preventing closure. Thus, manual tucking can be avoidedand retrieval forces can be removed. FIGS. 13A-13B illustrate theautomatic tucking of the cloth into the prosthesis 100.

As shown in FIG. 9, the ventricular portion (e.g., the bottom, distal,or lower portion) of the skirt 180 (e.g., fabric skirt) may act as a“curtain” around the inner frame 220. For example, the ventricularportion 182 of the outer skirt 180 is not attached to the outer frame140 as the outer frame 140 ends above this portion of the skirt 180.This portion 182 is also not attached to the inner frame 220 until thebottom of the skirt 180. Thus, the portion 182 of the outer skirt 180 iscircumferentially unattached, and is instead held generally in tensionbetween an inner surface of the outer frame 140 and the an outer surfaceof the ventricular or distal end of the inner frame 220. This allows theouter skirt 180 to flex or bend when radial pressure is applied to it.Thus, the outer skirt 180 has the flexibility to conform to a valveannulus, such as the mitral valve annulus, which can create an improvedseal between the prosthesis 100 and the annulus. This can be especiallyadvantageous as by having the curtain configuration and a reduced outerframe 140, the overall profile of the device can be reduced. Further, byeliminating the lower portion of the outer frame 140 (e.g., the portionthat would surround portion 182), the outer frame 140 can compress moreeasily against the inner frame 220 and the overall structure cancompress to a much smaller diameter as compared to a device having anouter frame extending all the way to the inner frame anchoring features124.

FIGS. 14A-B and 15 illustrate an embodiment of a prosthesis 100 whichcan improve the stiffness of the inner frame anchoring features 124using the outer skirt 180. In particular, the skirt 180 can be addedinto the prosthesis 100 to increase the stiffness of the inner frameanchoring features 124, for example by distributing force between theinner frame 120, the outer frame 140, and the added stiffness improvingmaterial 192 (which can be a portion of skirt 180). Thus, the stiffnessimproving material 192 can be incorporated into, or can be the same, asthe skirt 180 or can be its own separate material.

FIGS. 14A-B illustrate an example embodiment of the improved stiffness.As shown, the prosthesis can include the inner frame 120 having theinner frame anchoring features 124, the outer frame 140, and thestiffness improving material 192. In some embodiments, the stiffnessimproving material 192 can be cloth, fabric, or other soft material suchas discussed above with respect to skirt 180. As shown, the stiffnessimproving material 192 can be attached at three different points on theprosthesis 100. The stiffness improving material 192 can be locatedbetween the frames 120/140 our radially outwards of both frames 120/140.

At one point, the stiffness improving material 192 can be attached to alower end of the outer frame 140. This stiffness improving material 192can be attached at the base apices of struts 156 a or at the base apicesof struts 156 b. However, the stiffness improving material 192 can beattached at any particular point of the outer frame 140. In someembodiments, the stiffness improving material 192 can be attached toouter frame anchoring feature 144 if used. The attachment can besutures, threads, chemical adhesives, mechanical fastening, and theparticular attachment is not limiting.

Next, the stiffness improving material 192 can be attached on the innerframe anchoring features 124. For example, it can be attachedapproximately midway along the inner frame anchoring features 124, suchas shown in FIGS. 14A-B. However, the stiffness improving material 192can be attached at any point along the inner frame anchoring features124, and the particular location is not limiting. The attachment can begenerally at the midpoint of the stiffness improving material 192, butthis is not limiting. The attachment can be sutures, threads, chemicaladhesives, mechanical fastening, and the particular attachment is notlimiting.

Further, the second end of the stiffness improving material 192 can beattached to a portion of the inner frame 120. For example, it can beattached at the longitudinally extending strut 138 or at thecircumferentially extending struts 136 b. The stiffness improvingmaterial 192 can be attached at the first and second ends generally atthe same longitudinal position. At some embodiments, the stiffnessimproving material 192 is attached to the inner frame 120 at a differentlongitudinal position than where it is attached to the outer frame 140.In some embodiments, the stiffness improving material 192 is attached tothe inner frame 120 at a lower longitudinal position (e.g., towards theinner frame anchoring features 124) than where it is attached to theouter frame 140. In some embodiments, the stiffness improving material192 is attached to the inner frame 120 at a higher longitudinal position(e.g., away from the inner frame anchoring features 124) than where itis attached to the outer frame 140. The attachment can be sutures,threads, chemical adhesives, mechanical fastening, and the particularattachment is not limiting.

FIG. 14A shows the prosthesis 100 in the expanded position. As shown,the stiffness improving material 192 is pulled taught, thereby applyingan upward force on the stiffness improving material 192 and thus theinner frame anchoring features 124. Once the prosthesis 100 beginscompress, as shown in FIG. 14B, the stiffness improving material 192becomes slack, thus reducing the stiffness of the inner frame anchoringfeatures 124 and facilitating retrieval.

In some embodiments, the stiffness improving material 192 can extendalong a circumference of the prosthesis 100 such as discussed above withrespect to skirt 180. In some embodiments, the stiffness improvingmaterial 192 can extend partially around the circumference of theprosthesis 100. In some embodiments, multiple the stiffness improvingmaterial 192 can be used. In some embodiments, the stiffness improvingmaterial 192 is attached to every inner frame anchoring features 124. Insome embodiments, the stiffness improving material 192 is attached toevery other inner frame anchoring features 124. In some embodiments, thestiffness improving material 192 is attached to every third inner frameanchoring features 124.

Further, the use of the stiffness improving material 192 can create a“sealed void”, “clot pocket”, “cloth pocket”, or “pocket” between theinner frame 120 and the outer frame 140. The pocket is an empty volumecovered with the stiffness improving material 192 between the innerframe 120 and the outer frame 140. This can reduce thrombosis formationon the prosthesis 100 as in an open configuration blood can flow throughstruts in the frames and circulate between the frames causing thrombus.In some embodiments, there can be a number of holes in the stiffnessimproving material 192, and thus the stiffness improving material 192can inflate, clot over, and permanently stay inflated.

FIG. 15 illustrates an alternate stiffness improving material 192 wherethe stiffness improving material 192 is one or more sutures. As shown, asingle suture can extend around the circumference of the prosthesis 100,but in some embodiments multiple discrete sutures can be used. In thisembodiment, the sutures extend between outer frame anchoring features144 and circumferentially adjacent inner frame anchoring feature 124,thus forming a “zig-zag” pattern around the prosthesis 100. As shown,the stiffness improving material 192 can pass through apertures at theends of the outer frame anchoring features 144. The stiffness improvingmaterial 192 can either be tied in or pass through the apertures. Thestiffness improving material 192 can then attach to material around theinner frame anchoring feature 124. In some embodiments, the stiffnessimproving material 192 can wrap around the inner frame anchoringfeatures 124 themselves, such as forming a loop in the suture orextending through an aperture or around a protrusion in the inner frameanchoring feature 124. However, in some embodiments outer frameanchoring features 144 may not be used and the sutures can attachdirectly to the outer frame 140 such as discussed above.

Advantageously, the use of the stiffness improving material 192 of anyof the above embodiments can prevent the outer frame 140 from crimpinginside the inner frame 120. This can be done by providing sufficienttension with the stiffness improving material 192 to prevent insertionof lower portions of the outer frame 140 from entering the inner frame120.

Although the prosthesis 100 has been described as including an innerframe 120, an outer frame 140, a valve body 160, and a skirt 180, it isto be understood that the prosthesis 100 need not include allcomponents. For example, in some embodiments, the prosthesis 100 caninclude the inner frame 120, the outer frame 140, and the valve body 160while omitting the skirt 180. Moreover, although the components of theprosthesis 100 have been described and illustrated as separatecomponents, it is to be understood that one or more components of theprosthesis 100 can be integrally or monolithically formed. For example,in some embodiments, the inner frame 120 and the outer frame 140 can beintegrally or monolithically formed as a single component.

Additionally, the prosthesis 100 may only include a single frame. Forexample, just the inner frame 120, just the outer frame 140, or acombination of the two in a single frame. Thus, the concepts discussedabove, such as the hourglass shape, the strut/cell shape, etc. can beincorporated into a single frame prosthesis.

Moreover, the prosthesis 100 may be applicable to a prosthesis havingmore than just the inner frame 120 and the outer frame 140. Thus, theconcepts discussed above, such as the hourglass shape, the strut/cellshape, etc. can be incorporated into a prosthesis having 1, 2, 3, 4, 5,or 6 frames.

FIG. 16 illustrates an embodiment of the prosthesis 100 being radiallycompressed.

FIGS. 17A-17B illustrate embodiments of the prosthesis 100 with somemodifications which can be used in conjunction with any of theimplementations disclosed herein. As shown in the figures, the outerframe 140 can have a substantial angular change (e.g., bend or shoulder)between the upper region 146 and the intermediate region 148 and thelower region 150. In some embodiments, the bend could be 50, 60, 70, 80,90, or 100 degrees. In some embodiments, the bend could be greater than50, 60, 70, 80, 90, or 100 degrees. In some embodiments, the bend couldbe less than 50, 60, 70, 80, 90, or 100 degrees. In some embodiments,the lower region 150 may have approximately the same radial diameterthan the intermediate region 148. In some embodiments, the lower region150 may have smaller radial diameter than the intermediate region 148.This can, for example, allow the frame to act as a “plug” or “cork”within the mitral valve annulus. In some embodiments, the mitral valveannulus, or other structural heart features, may apply radially inwardpressure on the prosthesis 100, causing some indents, bends, orcompression of the intermediate region 148 or the lower region 150,which can allow the prosthesis 100 to achieve a tighter fit. Theprosthesis 100 can have a scalloped inflow. This can help reduce atrialprojection and promote flow prior to release from the delivery system.FIG. 17B illustrates an embodiment of an inner frame anchoring feature124. As shown, the distal tip can be covered by a first material 121,such as ePTFE or other plastic, while the main curve can be covered by asecond material 123. The second material 123 can be a foam or fabric. Insome embodiments, the second material 123 can be a PET-coveredpolyurethane foam, though this is not limiting. The two materials can beattached together, such as by suturing, shrinkage, friction, ormechanical fastening, or can be separate.

FIG. 29 illustrates an alternate embodiment of a prosthesis 100 whichcan include any or all of the features described herein. As shown, theouter frame 140 can have a bulbous (or generally bulbous shape). Forexample, the outer frame 140 can have a shoulder as shown in FIG. 29.

The different iterations of the prosthesis frame disclosed above, suchas, but not limited to, the ones shown in FIG. 1, FIG. 9, FIG. 12, FIG.17A, FIG. 21, FIG. 29, and FIG. 30A, can provide advantageous for theimplantation procedure. For example, as discussed below, the prosthesis100 expands from a compressed configuration to an expanded configurationduring delivery. This can be done in or around the mitral annulus. Whenthe outer frame 140, including any of the variations of the outer frame140 discussed above, is expanded, it can circumferentially press againsttissue on the circumference of the mitral annulus. This shape canprovide a form of retention to stop the prosthesis 100 from going intothe left ventricle in diastole, and generally stabilize the prosthesis100 in the mitral valve annulus. Thus, in some implementations theprosthesis 100 outer frame 140 may not fully expand, and may beminimally to partially compressed within the mitral annulus. In otherimplementations, the prosthesis 100 may fully expand, and be retainedwithin the left ventricle by the inner frame anchoring features and inthe left atrium by the bulbous shape, for example including theshoulders, of the outer frame 140. In some implementations, afterrelease of the prosthesis 100, it can be moved towards the leftventricle by the heart where it will then “cork” in the mitral annulus.

Valve Body

With reference next to the valve body 160 illustrated in FIG. 10, thevalve body 160 can be positioned within the inner frame 120. The valvebody 160 can be a replacement heart valve which includes a plurality ofvalve leaflets 262. The valve leaflets 262 can include a first edge,second edge, and tabs for attaching the valve leaflets 262 together atcommissures of the valve body 160. The tabs can be used to secure thevalve leaflets 262 to the inner frame 120. The first edge can be anarcuate edge and can be generally fixed in position relative to theframe 120. The second edge can be a freely moving edge which can allowthe valve body 160 to open and close.

The plurality of valve leaflets 262 can function in a manner similar tothe native mitral valve, or to any other valves in the vascular systemas desired. The plurality of valve leaflets 262 can open in a firstposition and then engage one another to close the valve in a secondposition. The plurality of valve leaflets 262 can be made to function asa one way valve such that flow in one direction opens the valve and flowin a second direction opposite the first direction closes the valve. Forexample, the valve body 160 can open allow to blood to flow through thevalve body 160 in a direction from an upper end to a lower end. Thevalve body 160 can close to inhibit blood flow through the valve body160 in a direction from the lower end to the upper end. In situationswhere the prosthesis 100 is oriented such that an upper end is aproximal end and a lower end is a distal end, the valve body 160 can bepositioned such that the valve body 160 can open to allow blood to flowthrough the valve body 160 in a proximal-to-distal direction and closeto inhibit blood flow in a distal-to-proximal direction. The valve body160 can be constructed so as to open naturally with the beating of theheart. For example, the valve body 160 can open during diastole andclose during systole. The valve body 160 can replace a damaged ordiseased native heart valve such as a diseased native mitral valve.

The valve body 160 can include a liner. The liner can be used to assistwith fluid flow through and/or around the prosthesis 100, such asthrough and around the inner frame 120 and the valve leaflets 262. Theliner can surround at least a portion of the valve leaflets 262 and beconnected to one or more of the valve leaflets 262. For example, the oneor more valve leaflets 262 can be attached to the liner along the firstedge of the valve leaflets 262.

The liner can be positioned within the interior of the inner frame 120and can form an inner wall of the prosthesis 100. For example, the linercan be positioned such that the liner is radially inward, relative tothe longitudinal axis of the prosthesis 100, from the struts 136 a-c ofthe inner frame 120. In this manner, the fluid pathway towards the valveleaflets 262 can be relatively smooth. It is also contemplated that theliner can at least be partially positioned along an exterior of theinner frame 120 and/or outer frame 140 such that at least a portion ofthe liner is radially outward, relative to the longitudinal axis of theprosthesis 100, from struts of the inner frame 120 and/or outer frame140. The liner can be positioned along an upper or inlet side of theinner frame 120. The liner can extend from the first edge of the valveleaflets 262 towards the upper end of the inner frame 120. The liner canalso extend below the first edge of the valve leaflet 262 towards thelower end of the inner frame 120. The liner can also be made to movewith foreshortening portions of the inner frame 120.

In some embodiments, the liner can extend the entire length of the innerframe 120 or the inner frame body 122. In other embodiments, it canextend along only part of the length of the inner frame body 122 asshown. In some embodiments, the ends of the valve leaflets 262 cancoincide with ends of the liner. In addition, one or more of the ends ofthe inner frame body 122 can coincide with the ends of the liner. An endof the liner can be positioned between the upper end of the inner frame120 and the valve leaflets 262. The end of the liner can extend above anupper end of the inner frame body 122 and extend along a portion of thelocking tabs. In some embodiments, the end of the liner can bepositioned at or proximate an uppermost portion of the first or arcuateedge of the valve leaflet 262 below the upper end of the inner framebody 122.

Other shapes and configurations can also be used for the valve body 160.In some embodiments, the liner may extend along the length of theleaflets, but is not connected to them. In the illustrated embodiment,the liner is attached to the inner frame 120 and at least a portion ofthe leaflets 262, such as the first or arcuate edge, is attached to theliner. Portions of the valve leaflets 262, such as the portions of thefirst edge and/or tabs, can also be attached to the inner frame 120. Theliner and/or the valve leaflets 262 can be attached to the inner frame120 or to each other using any of the fasteners and/or techniquesdescribed herein including, but not limited to, mechanical fasteners,such as sutures, staples, screws, rivets, interfacing members (e.g.,tabs and slots), and any other type of mechanical fastener as desired,chemical fasteners such as adhesives and any other type of chemicalfastener as desired, fastening techniques such as welding, soldering,sintering, and any other type of fastening technique as desired, and/ora combination of such fasteners and techniques.

The liner can be constructed in multiple different ways. The liner canbe made a layer of resilient material, such as such as knit polyester(e.g., polyethylene terephthalate (PET), polyvalerolactone (PVL)) or anyother biocompatible material such as those which are wholly orsubstantially fluid impermeable, flexible, stretchable, deformable,and/or resilient. In some embodiments, the liner can be made from amaterial that is more flexible than the valve leaflet material. Theupper and/or lower end of the liner can be straight, curved, or have anyother desired configuration. For example, as shown in the illustratedembodiment, the liner can have a straight edge forming the end. In otherembodiments, the end can be patterned to generally correspond to theundulations at one end of the inner frame 120. The liner can be formedof one piece or multiple pieces.

In another embodiment of the liner, the end can extend past the innerframe 120 and can be wrapped around it. Thus, the liner can extend fromthe interior of the inner frame 120 to the exterior of the inner frame120. The liner can extend completely around the inner frame 120 for ¼,⅓, ½, or more of the length of inner frame 120.

Methods of placement and delivery of the prosthesis 100 can be found inU.S. Patent Publication No. 2018/005629, which is hereby incorporated byreference in its entirety.

Additional Valve Prostheses

FIGS. 18A-20 illustrate alternative embodiments of a prosthesis that canused with the disclosed delivery systems 10 and methodology discussedherein. FIGS. 18A-20 illustrates another alternate embodiment of aprosthesis, which is similar to the prosthesis described with respect toFIG. 33-35 of U.S. Pat. Pub. No. 2018/0055629, except that an outerframe anchoring feature is described in this publication. The entiretyof U.S. Pat. Pub. No. 2018/0055629, including the description relatingto FIGS. 33-35 as well as all other description relating to theprosthesis, delivery system and methods, are hereby incorporated byreference. The embodiments of FIGS. 18A-20 can have similar or the samefeatures to the other prostheses discussed herein. In some embodiments,the prosthesis may be a single frame prosthesis. In some embodiments,the prosthesis may be a dual frame prosthesis. In some embodiments foruse as a replacement mitral valve, the prosthesis includes distal orventricular anchors similar to those described above (see, for example,anchoring feature 1524 described below), but does not include proximalor atrial anchors.

With reference next to FIG. 18A, an embodiment of a prosthesis 1500 inan expanded configuration is illustrated. The prosthesis 1500 caninclude an inner frame 1520, an outer frame 1540, a valve body 1560, andone or more skirts, such as an outer skirt 1580 and an inner skirt 1590.

With reference first to the inner frame 1520, the inner frame 1520 caninclude an inner frame body 1522 and an inner frame anchoring feature1524. The inner frame body 1522 can have an upper region 1522 a, anintermediate region 1522 b, and a lower region 1522 c. As shown, theinner frame body 1522 can have a generally bulbous shape such that thediameters of the upper region 1522 a and the lower region 1522 c areless than the diameter of the intermediate region 1522 b. The diameterof the upper region 1522 a can be less than the diameter of the lowerregion 1522 c. This can beneficially allow the use of a smaller valvebody 1560 within the inner frame 1520 while allowing the inner framebody 1522 to have a larger diameter proximate the connection between theinner frame body 1522 and the inner frame anchoring feature 1524. Thislarger diameter can reduce the radial distance between the connectionand the tip or end of the inner frame anchoring feature 1524. This canbeneficially enhance fatigue resistance of the inner frame anchoringfeature 1524 by reducing the length of the cantilever.

While the illustrated inner frame body 1522 is bulbous, it is to beunderstood that the diameters of the upper region 1522 a, theintermediate region 1522 b, and/or the lower region 1522 c can be thesame such that the inner frame body 1522 can have more of a constantcross-sectional dimension along one or more regions. Moreover, while theillustrated embodiment includes a lower region 1522 a having a greaterdiameter than the upper region 1522 c, it is to be understood that thediameters of the upper and lower regions 1522 a, 1522 c can be the sameor the diameter of the upper region 1522 a can be greater than thediameter of the lower region 1522 c. Moreover, although the inner framebody 1522 has been described and illustrated as being cylindrical orhaving circular cross-sections, it is to be understood that all or aportion of the inner frame body 1522 can have a non-circularcross-section such as, but not limited to, a D-shape, an oval or anotherwise ovoid cross-sectional shape.

With reference next to the outer frame 1540 illustrated in FIG. 18A, theouter frame 1540 can be attached to the inner frame 1520 using anysuitable fastener and/or other technique. Although the outer frame 1540is illustrated as a separate component from the inner frame 1520, it isto be understood that the frames 1520, 1540 can be unitarily ormonolithically formed.

As shown in the illustrated embodiment, the outer frame 1540 can includean outer frame body 1542. The outer frame body 1542 can have an upperregion 1542 a, an intermediate region 1542 b, and a lower region 1542 c.When in an expanded configuration such as a fully expandedconfiguration, the outer frame body 1542 can have an enlarged shape withthe intermediate region 1542 b and the lower region 1542 c being largerthan the upper region 1542 a. The enlarged shape of the outer frame body1542 can advantageously allow the outer frame body 1542 to engage anative valve annulus, native valve leaflets, or other tissue of the bodycavity, while spacing the upper end from the heart or vessel wall.

The upper region 1542 a of the outer frame body 1542 can include a firstsection 1546 a and a second section 1546 b. The first section 1546 a canbe sized and/or shaped to generally match the size and/or shape of theinner frame 1520. For example, the first section 1546 a can have acurvature which matches a curvature of the upper region 1522 a of theinner frame body 1522. The second section 1546 b can extend radiallyoutwardly away from the inner frame 1520. As shown in the illustratedembodiment, the transition between the first section 1546 a and thesecond section 1546 b can incorporate a bend such that the secondsection 1546 b extends radially outwardly at a greater angle relative tothe longitudinal axis.

The intermediate region 1542 b of the outer frame body 1542 can extendgenerally downwardly from the outwardly-extending section 1546 b of theupper region 1542 a. As shown, the intermediate region 1542 b can have agenerally constant diameter from an upper end to a lower end such thatthe intermediate region 1542 b forms a generally cylindrical shape. Thelower region 1542 c of the outer frame body 1542 can extend generallydownwardly from the lower end of the intermediate region 1542 b. Asshown, the lower region 1542 c of the outer frame body 1542 can have agenerally constant diameter from an upper end to a lower end such thatthe lower region 1542 c forms a generally cylindrical shape. As shown,the diameters of the intermediate region 1542 b and the lower region1542 c are generally equivalent such that the intermediate region 1542 band the lower region 1542 c together form a generally cylindrical shape.

While the intermediate and lower regions 1542 b, 1542 c have beendescribed as cylindrical, it is to be understood that the diameters ofthe upper end, the lower end, and/or the portion therebetween can bedifferent. For example, a diameter of the portion between the upper endand the lower end can be larger than the upper end and the lower endsuch that the intermediate region 1542 b and/or lower region 1542 cforms a generally bulbous shape. In some embodiments, the diameter ofthe lower end can be larger than the diameter of the upper end. In otherembodiments, the diameter of the upper end can be larger than thediameter of the lower end. Moreover, although the outer frame body 1542has been described and illustrated as being cylindrical or havingcircular cross-sections, it is to be understood that all or a portion ofthe outer frame body 1542 can be have a non-circular cross-section suchas, but not limited to, a D-shape, an oval or an otherwise ovoidcross-sectional shape.

The outer frame 1540, such as the outer frame body 1542 can be used toattach or secure the prosthesis 1500 to a native valve, such as a nativemitral valve. For example, the intermediate region 1542 b of the outerframe body 1542 can be positioned to contact or engage a native valveannulus, tissue beyond the native valve annulus, native leaflets, and/orother tissue at or around the implantation location during one or morephases of the cardiac cycle, such as systole and/or diastole. As anotherexample, the outer frame body 1542 can be sized and positioned relativeto the inner frame anchoring feature 1524 such that tissue of the bodycavity positioned between the outer frame body 1542 and the inner frameanchoring feature 1524, such as native valve leaflets and/or a nativevalve annulus, can be engaged or pinched to further secure theprosthesis 1500 to the tissue.

With continued reference to the prosthesis 1500 illustrated in FIG. 18A,the valve body 1560 is attached to the inner frame 1520 within aninterior of the inner frame body 1522. The valve body 1560 functions asa one-way valve to allow blood flow in a first direction through thevalve body 1560 and inhibit blood flow in a second direction through thevalve body 1560.

The valve body 1560 can include a plurality of valve leaflets 1562, forexample three leaflets 1562, which are joined at commissures. The valvebody 1560 can include one or more intermediate components 1564. Theintermediate components 1564 can be positioned between a portion of, orthe entirety of, the leaflets 1562 and the inner frame 1520 such that atleast a portion of the leaflets 1542 are coupled to the frame 1520 viathe intermediate component 1564. In this manner, a portion of, or theentirety of, the portion of the valve leaflets 1562 at the commissuresand/or an arcuate edge of the valve leaflets 1562 are not directlycoupled or attached to the inner frame 1520 and are indirectly coupledor “float” within the inner frame 1520. For example, a portion of, orthe entirety of, the portion of the valve leaflets 1562 proximate thecommissures and/or the arcuate edge of the valve leaflets 1562 can bespaced radially inward from an inner surface of the inner frame 1520. Byusing one or more intermediate components 1564, the valve leaflets 1562can be attached to non-cylindrical frames 1520 and/or frames 1520 havinga diameter larger than that of the diameter of the valve leaflets 1562.

With reference next to the outer skirt 1580 illustrated in FIG. 18A, theouter skirt 1580 can be attached to the inner frame 1520 and/or outerframe 1540. As shown, the outer skirt 1580 can be positioned around andsecured to a portion of, or the entirety of, the exterior of the outerframe 1540. The skirt 1580 can also be secured to a portion of the valvebody 1560 such as, but not limited to, the intermediate components 1564.For example, the skirt 1580 can be attached to an inflow region of theintermediate components 1564. As shown, the outer skirt 1580 can followthe contours of the outer frame 1540; however, it is to be understoodthat at least a portion of the skirt 1580 can be spaced apart from atleast a portion of both the inner frame 1520 and the outer frame 1540.

With reference next to the inner skirt 1590 illustrated in FIG. 18A, theinner skirt 1590 can be attached to the valve body 1560 and the outerskirt 1580. As shown, a first end of the inner skirt 1590 can be coupledto the valve body 1560 along portions of the valve body 1560 which areproximate the inner frame 1520. A second end of the inner skirt 1590 canbe attached to the lower region of the outer skirt 1580. In so doing, asmooth surface can be formed under each of the leaflets. This canbeneficially enhance hemodynamics by allowing blood to more freelycirculate and reducing areas of stagnation. In some embodiments, theinner skirt 1590 can beneficially reduce contact between the outer framebody 1542 and the inner frame body 1522.

Although the prosthesis 1500 has been described as including an innerframe 1520, an outer frame 1540, a valve body 1560, and skirts 1580,1590, it is to be understood that the prosthesis 1500 need not includeall components. For example, in some embodiments, the prosthesis 1500can include the inner frame 1520, the outer frame 1540, and the valvebody 1560 while omitting the skirt 1580. Moreover, although thecomponents of the prosthesis 1500 have been described and illustrated asseparate components, it is to be understood that one or more componentsof the prosthesis 1500 can be integrally or monolithically formed. Forexample, in some embodiments, the inner frame 1520 and the outer frame1540 can be integrally or monolithically formed as a single component.

FIG. 18B illustrates an alternate embodiment of FIG. 18A withmodifications to the design of the skirts (or cloth) 1580/1590. Asshown, the skirts 1580/1590 can contact both the inner frame 1520 andouter frame 1540. The skirts 1580/1590 can start on the inside of theouter 1540, transition to the outside of the outer frame 1540, thenattach to the bottom of the outside of the inner frame 1520, thenproceed up along the outside of the inner frame 1520. By closing theskirts 1580/1590, this could avoid/reduce clot formation/embolization.

With reference next to FIGS. 19-20, an embodiment of a prosthesis 1600in an expanded configuration is illustrated. This prosthesis 1600 may besimilar in construction to the prosthesis 1500 described above. Theprosthesis 1600 can include an inner frame 1620, an outer frame 1640, avalve body 1660, and one or more skirts, such as an outer skirt 1680 andan inner skirt 1690.

With reference first to the outer frame 1640 illustrated in FIGS. 19-20,the outer frame 1640 can be attached to the inner frame 1620 using anyknown fasteners and/or techniques. Although the outer frame 1640 isillustrated as a separate component from the inner frame 1620, it is tobe understood that the frames 1620, 1640 can be unitarily ormonolithically formed.

As shown in the illustrated embodiment, the outer frame 1640 can includean outer frame body 1642. The outer frame body 1642 can have an upperregion 1642 a, an intermediate region 1642 b, and a lower region 1642 c.At least a portion of the upper region 1642 a of the outer frame body1642 can be sized and/or shaped to generally match the size and/or shapeof an upper region 1622 a of the inner frame 1620. As shown in theillustrated embodiment, the upper region 1642 a of the outer frame body1642 can include one or more struts which generally match the sizeand/or shape of struts of the inner frame 1620. This can locallyreinforce a portion of the prosthesis 1600 by effectively increasing thewall thickness of the combined struts.

When in an expanded configuration such as in a fully expandedconfiguration, the outer frame body 1642 can have a shape similar tothat of outer frame body 1542 described above in connection with FIG.18A. As shown, the intermediate region 1642 b and the lower region 1642c can have a diameter which is larger than the diameter of the upperregion 1642 a. The upper region 1642 a of the outer frame body 1642 canhave a decreasing diameter from a lower end to an upper end such thatthe upper region 1642 a is inclined or curved radially inwards towardsthe longitudinal axis of the prosthesis 1600. Although the outer framebody 1642 has been described and illustrated as being cylindrical orhaving circular cross-sections, it is to be understood that all or aportion of the outer frame body 1642 can be have a non-circularcross-section such as, but not limited to, a D-shape, an oval or anotherwise ovoid cross-sectional shape.

With continued reference to the outer frame 1600 illustrated in FIG. 19,the outer frame body 1642 can include a plurality of struts with atleast some of the struts forming cells 1646 a-c. Any number ofconfigurations of struts can be used, such as rings of undulating strutsshown forming ellipses, ovals, rounded polygons, and teardrops, but alsochevrons, diamonds, curves, and various other shapes.

The upper row of cells 1646 a can have an irregular octagonal shape suchas a “heart” shape. This additional space can beneficially allow theouter frame 1640 to retain a smaller profile when crimped. The cell 1646a can be formed via a combination of struts. As shown in the illustratedembodiment, the upper portion of cells 1646 a can be formed from a setof circumferentially-expansible struts 1648 a having a zig-zag orundulating shape forming a repeating “V” shape. The struts 1648 a canextend radially outwardly from an upper end to a lower end. These strutscan generally match the size and/or shape of struts of the inner frame1620.

The middle portion of cells 1646 a can be formed from a set of struts1648 b extending downwardly from bottom ends of each of the “V” shapes.The struts 1648 b can extend radially outwardly from an upper end to alower end. The portion of the cells 1646 a extending upwardly from thebottom end of struts 1648 b may be considered to be a substantiallynon-foreshortening portion of the outer frame 1640.

The lower portion of cells 1646 a can be formed from a set ofcircumferentially-expansible struts 1648 c having a zig-zag orundulating shape forming a repeating “V” shape. As shown in theillustrated embodiment, the struts 1648 c can incorporate a curvaturesuch that the lower end of struts 1648 c extend more parallel with thelongitudinal axis than the upper end of the struts 1648 c. One or moreof the upper ends or tips of the circumferentially-expansible struts1648 c can be a “free” apex which is not connected to a strut. Forexample, as shown in the illustrated embodiment, every other upper endor tip of circumferentially-expansible struts 1648 b is a free apex.However, it is to be understood that other configurations can be used.For example, every upper apex along the upper end can be connected to astrut.

The middle and/or lower rows of cells 1646 b-c can have a differentshape from the cells 1646 a of the first row. The middle row of cells1646 b and the lower row of cells 1646 c can have a diamond or generallydiamond shape. The diamond or generally diamond shape can be formed viaa combination of struts.

The upper portion of cells 1646 b can be formed from the set ofcircumferentially-expansible struts 1648 c such that cells 1646 b sharestruts with cells 1646 a. The lower portion of cells 1646 b can beformed from a set of circumferentially-expansible struts 1648 d. Asshown in the illustrated embodiment, one or more of thecircumferentially-expansible struts 1648 d can extend generally in adownward direction generally parallel to the longitudinal axis of theouter frame 1640.

The upper portion of cells 1646 c can be formed from the set ofcircumferentially-expansible struts 1648 d such that cells 1646 c sharestruts with cells 1646 b. The lower portion of cells 1646 c can beformed from a set of circumferentially-expansible struts 1648 e.Circumferentially-expansible struts 1648 e can extend generally in adownward direction.

As shown in the illustrated embodiment, there can be a row of nine cells1646 a and a row of eighteen cells 1646 b-c. While each of the cells1646 a-c are shown as having the same shape as other cells 1646 a-c ofthe same row, it is to be understood that the shapes of cells 1646 a-cwithin a row can differ. Moreover, it is to be understood that anynumber of rows of cells can be used and any number of cells may becontained in the rows.

As shown in the illustrated embodiment, the outer frame 1600 can includea set of eyelets 1650. The upper set of eyelets 1650 can extend from anupper region 1642 a of the outer frame body 1642. As shown, the upperset of eyelets 1650 can extend from an upper portion of cells 1646 a,such as the upper apices of cells 1646 a. The upper set of eyelets 1650can be used to attach the outer frame 1640 to the inner frame 1620. Forexample, in some embodiments, the inner frame 1620 can include one ormore eyelets which correspond to the eyelets 1650. In such embodiments,the inner frame 1620 and outer frame 1640 can be attached together viaeyelets 1650 and corresponding eyelets on the inner frame 1620. Forexample, the inner frame 1620 and outer frame 1640 can be suturedtogether through said eyelets or attached via other means, such asmechanical fasteners (e.g., screws, rivets, and the like).

As shown, the set of eyelets 1650 can include two eyelets extending inseries from each “V” shaped strut. This can reduce the likelihood thatthe outer frame 1640 twists along an axis of the eyelet. However, it isto be understood that some “V” shaped struts may not include an eyelet.Moreover, it is to be understood that a fewer or greater number ofeyelets can extend from a “V” shaped strut.

The outer frame 1640 can include a set of locking tabs 1652 extendingfrom at or proximate an upper end of the upper region 1642 a. As shown,the locking tabs 1652 can extend upwardly from the set of eyelets 1650.The outer frame 1640 can include twelve locking tabs 1652, however, itis to be understood that a greater number or lesser number of lockingtabs can be used. The locking tabs 1652 can include alongitudinally-extending strut 1652 a. At an upper end of the strut 1652a, the locking tab 1652 can include an enlarged head 1652 b. As shown,the enlarged head 1652 b can have a semi-circular or semi-ellipticalshape forming a “mushroom” shape with the strut 1652 a. The locking tab1652 can include an eyelet 1652 c which can be positioned through theenlarged head 1652 b. It is to be understood that the locking tab 1652can include an eyelet at other locations, or can include more than asingle eyelet.

The locking tab 1652 can be advantageously used with multiple types ofdelivery systems. For example, the shape of the struts 1652 a and theenlarged head 1652 b can be used to secure the outer frame 1640 to a“slot” based delivery system, such as the inner retention member 40described above. The eyelets 1652 c and/or eyelets 1650 can be used tosecure the outer frame 1640 to a “tether” based delivery system such asthose which utilize sutures, wires, or fingers to control delivery ofthe outer frame 1640 and the prosthesis 1600. This can advantageouslyfacilitate recapture and repositioning of the outer frame 1640 and theprosthesis 1600 in situ.

The outer frame 1640, such as the outer frame body 1642 can be used toattach or secure the prosthesis 1600 to a native valve, such as a nativemitral valve. For example, the intermediate region 1642 b of the outerframe body 1642 and/or the outer anchoring feature 1644 can bepositioned to contact or engage a native valve annulus, tissue beyondthe native valve annulus, native leaflets, and/or other tissue at oraround the implantation location during one or more phases of thecardiac cycle, such as systole and/or diastole. As another example, theouter frame body 1642 can be sized and positioned relative to the innerframe anchoring feature 1624 such that tissue of the body cavitypositioned between the outer frame body 1642 and the inner frameanchoring feature 1624, such as native valve leaflets and/or a nativevalve annulus, can be engaged or pinched to further secure theprosthesis 1600 to the tissue. As shown, the inner frame anchoringfeature 1624 includes nine anchors; however, it is to be understood thata fewer or greater number of anchors can be used. In some embodiments,the number of individual anchors can be chosen as a multiple of thenumber of commissures for the valve body 1660. For example, for a valvebody 1660 have three commissures, the inner frame anchoring feature 1624can have three individual anchors (1:1 ratio), six individual anchors(2:1 ratio), nine individual anchors (3:1 ratio), twelve individualanchors (4:1 ratio), fifteen individual anchors (5:1 ratio), or anyother multiple of three. In some embodiments, the number of individualanchors does not correspond to the number of commissures of the valvebody 1660.

With continued reference to the prosthesis 1600 illustrated in FIGS.19-20, the valve body 1660 is attached to the inner frame 1620 within aninterior of the inner frame body 1622. The valve body 1660 functions asa one-way valve to allow blood flow in a first direction through thevalve body 1660 and inhibit blood flow in a second direction through thevalve body 1660.

The valve body 1660 can include a plurality of valve leaflets 1662, forexample three leaflets 1662, which are joined at commissures. The valvebody 1660 can include one or more intermediate components 1664. Theintermediate components 1664 can be positioned between a portion of, orthe entirety of, the leaflets 1662 and the inner frame 1620 such that atleast a portion of the leaflets 1642 are coupled to the frame 1620 viathe intermediate component 1664. In this manner, a portion of, or theentirety of, the portion of the valve leaflets 1662 at the commissuresand/or an arcuate edge of the valve leaflets 1662 are not directlycoupled or attached to the inner frame 1620 and are indirectly coupledor “float” within the inner frame 1620.

With reference next to the outer skirt 1680 illustrated in FIG. 19, theouter skirt 1680 can be attached to the inner frame 1620 and/or outerframe 1640. As shown, the outer skirt 1680 can be positioned around andsecured to a portion of, or the entirety of, the exterior of the outerframe 1640. The inner skirt 1690 can be attached to the valve body 1660and the outer skirt 1680. As shown in FIG. 40, a first end of the innerskirt 1690 can be coupled to the valve body 1660 along portions of thevalve body 1660 which are proximate the inner frame 1620. A second endof the inner skirt 1690 can be attached to the lower region of the outerskirt 1680. In so doing, a smooth surface can be formed along under eachof the leaflets. This can beneficially enhance hemodynamics by allowingblood to more freely circulate and reducing areas of stagnation.

Although the prosthesis 1600 has been described as including an innerframe 1620, an outer frame 1640, a valve body 1660, and skirts 1680,1690, it is to be understood that the prosthesis 1600 need not includeall components. For example, in some embodiments, the prosthesis 1600can include the inner frame 1620, the outer frame 1640, and the valvebody 1660 while omitting the skirt 1680. Moreover, although thecomponents of the prosthesis 1600 have been described and illustrated asseparate components, it is to be understood that one or more componentsof the prosthesis 1600 can be integrally or monolithically formed. Forexample, in some embodiments, the inner frame 1620 and the outer frame1640 can be integrally or monolithically formed as a single component.

FIG. 21 illustrates an embodiments of the frame of prosthesis 1600 whichcan have two different sizes. The prostheses 1600 may just be scaled forsize, and there are no substantive/functional differences between thetwo. Prosthesis 100 can also be made of various sizes.

FIG. 22 shows the inner frame 1520 of prosthesis 1600 and FIG. 23 showsthe outer frame 1540 of prosthesis 1600.

FIG. 24 illustrates a distal end of an inner frame anchoring feature1624 of prosthesis 1600, though the same structure can be used for anyof the prostheses 100 disclosed herein. As shown, the distal tip 1625 ofthe inner frame anchoring feature 1624 can include two struts 1627ending with generally L-shaped anchors 1629 that face circumferentiallyopposite directions. As shown, the L-shaped anchors 1629 are notcircumferentially aligned so that each L-shaped anchor 1629 has a freeend. For example, a first of the struts 1627 can bend radially inward ascompared to a second of the struts 1627. The L-shaped anchors 1629 canbe spaced 1, 2, 3, 4, 5, or 6 mm away from each other. In someembodiments, more struts 1627 and more anchors 1629 can be used. TheL-shaped anchors 1629 provide for a greater area of attachment of anycushions/sutures, thereby preventing slippage or movement of thecushions.

Anchor Separator

FIGS. 25A-27B illustrate embodiments of an anchor separator that can beused with any of the above-described embodiments of prostheses.

In some loading procedures, the inner frame anchoring features disclosedherein may not load uniformly, but instead cross or spiral as they load.This non-uniform loading can be disadvantageous as it can causenon-uniform straining of the inner frame anchoring feature, which maymake the prosthesis more prone to fracturing or cracking. Thenon-uniform loading can also cause increases in valve loading and/ordeployment forces, which may cause further loads on the frame, on softtissue, or on fabric/suturing components.

Accordingly, FIGS. 25A-25B illustrate an embodiment of an anchorseparator 2500. As shown, the anchor separator 2500 can be a body 2502having a lumen 2504 extending generally along a longitudinal centerlineof the body 2502, and can include a plurality of longitudinallyextending groves 2506 formed by a plurality of extensions 2508 on anouter radial surface of the body 2502. The body 2502 can be generallytubular with the extensions 2508 extending radially off of the tubularbody 2502.

As shown, the extensions 2508 can be generally triangular shaped havinga base of the triangle being the outer radialmost position, though theparticular shape is not limiting. Adjacent extensions 2508 formgenerally rectangular grooves 2506 or slots between them along alongitudinal length of the body 2502 configured to receive the innerframe anchoring features 1624. In some embodiments, theextensions/grooves 2508/2506 can extend fully along a longitudinallength of the body 2502. In some embodiments, the extensions/grooves2508/2506 can extend 95%, 90%, 85%, 80%, or 75% of a longitudinal lengthof the body 2502. In some embodiments, the extensions/grooves 2508/2506can extend greater than 95%, 90%, 85%, 80%, or 75% of a longitudinallength of the body 2502. In some embodiments, the extensions/grooves2508/2506 can extend less than 95%, 90%, 85%, 80%, or 75% of alongitudinal length of the body 2502.

In some embodiments, the body 2502 can have 3, 4, 5, 6, 7, 8, 9, 10, 11,or 12 grooves 2506. In some embodiments, the body 2502 can have greaterthan 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 grooves 2506. In someembodiments, the body can have less than 3, 4, 5, 6, 7, 8, 9, 10, 11, or12 grooves 2506. In some embodiments, the body 2502 can have the sameamount of grooves 2506 as the prosthesis has inner frame anchoringfeatures 1624. In some embodiments, the body 2502 can have fewer grooves2506 than the replacement valve has inner frame anchoring features 1624.In some embodiments, the body 2502 can have more grooves 2506 than thereplacement valve has inner frame anchoring features 1624.

In some embodiments, such as shown in FIGS. 25A-25B, the body 2502 canbe tapered radially inwards towards the proximal and distal ends of thebody 2502 (e.g., generally along a longitudinal axis). Further, asshown, the extensions 2508 can similarly be radially tapered inwards onthe proximal and distal ends. This can reduce or prevent the separator2500 from catching on the deployed prostheses when the delivery systemis retracted through the prosthesis.

Accordingly, the inner frame anchoring features can be releasably loadedinto the grooves 2506 to prevent them from twisting, rotating, moving,or displacing out of plane. The inner frame anchoring features can beretained in the grooves 2506 by a radially outer sheath, and when thesheath is removed the inner frame anchoring features 1624 can releasefrom the grooves 2506. An example prosthesis is shown in FIG. 26 withanchoring features 1624 (but similarly could be used for 124) insertedinto the separator 2500. The inner frame anchoring features can beloaded uniformly around a circumference of the separator 2500. FIGS.27A-27B illustrate the separator 2500 used with a delivery system, suchas delivery system 10 disclosed below.

In some embodiment, the separator 2500 can slide along a shaft, such asthe nosecone shaft of the delivery system described in US Pat. App. Pub.Nos. 2017/0056169, 2016/0317301, 2017/0056171, 2019/0008640, theentirety of each of which is hereby incorporated by reference. In someembodiments, the separator 2500 can be fixed to the shaft. In someembodiments, the separator 2500 can have an axial/longitudinal degree offreedom along the shaft. In some embodiments, the separator 2500 canhave a rotational degree of freedom along the shaft. Preferably, theseparator 2500 can be axially fixed but can have free rotation. This canallow the separator 2500 to be adjusted as the prosthesis gets pulledinside the delivery system catheter, thereby aligning all of the innerframe anchoring features circumferentially. In some embodiments, theseparator 2500 may not be attached to the delivery system.

Delivery System Suture Attachment

FIGS. 28A-28B illustrate a prosthesis 100, including any discussedabove, having a suture 2802 configured to attach to a delivery system,such as the one discussed below. For example, fingers, knobs, or shaftsin the delivery system may releasable hold onto the suture 2802. In someembodiments, the delivery system can include an additional suture forconnecting to suture 2802, such as shown in FIG. 28B. The additionalsuture 2804 can wrap around and/or intertwine with suture 2802 toconnect the prosthesis 100 to the delivery system.

The suture 2802 can be permanently attached to the prosthesis 100 or canbe removed upon delivery. In some embodiments, the suture 2802 can bebiodegradable.

As shown, the suture 2802 can generally extend around an outercircumference of the atrial end of the prosthesis 100. In someembodiments, the suture 2802 can extend fully or partially around thecircumference. The suture 2802 can be attached to the prosthesis 100 ina number of ways. In some embodiments, the suture 2802 can pass throughthe eyelets 120 in the outer frame. The suture 2802 can pass through allor some of the eyelets 120. In some embodiments, the suture 2802 canwrap or otherwise attach to the tabs 104 of the inner frame. In someembodiments, the suture 2802 can attach to both the outer frame and theinner frame. In some embodiments, the suture 2802 can be compressedbetween the two frames. In some embodiments, the suture 2802 can beattached, such as chemically or mechanically, to the prosthesis 100.

Delivery System

FIG. 35 illustrates an embodiment of a delivery device, system, orassembly 10, such as described in U.S. Pat. Pub. No. 2019/0008640,hereby incorporated by reference in its entirety. The delivery system 10can be used to deploy a prosthesis, such as a replacement heart valve,within the body. In some embodiments, the delivery system 10 can use adual plane deflection approach to properly delivery the prosthesis.Replacement heart valves can be delivered to a patient's heart mitralvalve annulus or other heart valve location in various manners, such asby open surgery, minimally-invasive surgery, and percutaneous ortranscatheter delivery through the patient's vasculature. Exampletransfemoral approaches may be found in U.S. Pat. Pub. No. 2015/0238315,filed Feb. 20, 2015, the entirety of which is hereby incorporated byreference in its entirety. While the delivery system 10 is described inconnection with a percutaneous delivery approach, and more specificallya transfemoral delivery approach, it should be understood that featuresof delivery system 10 can be applied to other delivery system, includingdelivery systems for a transapical delivery approach.

The delivery system 10 can be used to deploy a prosthesis, such as areplacement heart valve as described elsewhere in this specification,within the body. The delivery system 10 can receive and/or coverportions of the prosthesis such as a first end (e.g., atrial end) andsecond end (e.g., ventricular end) of the prosthesis 100. For example,the delivery system 10 may be used to deliver an expandable implant orprosthesis 100, where the prosthesis 100 includes the first end and thesecond end, and wherein the second end is configured to be deployed orexpanded before the first end. Discussion of the attachment of theprosthesis 100 to the delivery system 10 can be found in U.S.Publication No. 2015/0328000A1, hereby incorporated by reference in itsentirety. Further details and embodiments of a replacement heart valveor prosthesis and its method of implantation are described in U.S.Publication Nos. 2015/0328000 and 2016/0317301 the entirety of each ofwhich is hereby incorporated by reference and made a part of thisspecification.

The delivery system 10 can be relatively flexible. In some embodiments,the delivery system 10 is particularly suitable for delivering areplacement heart valve to a mitral valve location through a transseptalapproach (e.g., between the right atrium and left atrium via atransseptal puncture).

As shown in FIG. 35, the delivery system 10 can include a shaft assembly12 comprising a proximal end 11 and a distal end 13, wherein a handle 14is coupled to the proximal end of the assembly 12. The shaft assembly 12can be used to hold the prosthesis for advancement of the same throughthe vasculature to a treatment location. The delivery system 10 canfurther comprise a relatively rigid live-on (or integrated) sheath 51surrounding the shaft assembly 12 that can prevent unwanted motion ofthe shaft assembly 12. The live-on sheath 51 can be attached at aproximal end of the shaft assembly 12 proximal to the handle 14, forexample at a sheath hub. The shaft assembly 12 can include an implantretention area at its distal end that can be used for this purpose. Insome embodiments, the shaft assembly 12 can hold an expandableprosthesis in a compressed state at implant retention area foradvancement of the prosthesis 100 within the body. The shaft assembly 12may then be used to allow controlled expansion of the prosthesis 100 atthe treatment location. In some embodiments, the shaft assembly 12 maybe used to allow for sequential controlled expansion of the prosthesis100. In some embodiments, the prosthesis 100 may be rotated in theimplant retention area.

As discussed in U.S. Pat. Pub. No. 2019/0008640, the distal end of thedelivery system 10 can include one or more subassemblies such as anouter sheath assembly, a mid shaft assembly, a rail assembly, an innershaft assembly, and a nose cone assembly. In some embodiments, thedelivery system 10 may not have all of the assemblies disclosed herein.For example, in some embodiments a full mid shaft assembly may not beincorporated into the delivery system 10.

In particular, embodiments of the disclosed delivery system 10 canutilize a steerable rail in the rail assembly for steering the distalend of the delivery system 10, allowing the implant to be properlylocated in a patient's body. The steerable rail can be, for example, arail shaft that extends through the delivery system 10 from the handle14 generally to the distal end. In some embodiments, the steerable railhas a distal end that ends proximal to the implant retention area. Auser can manipulate the bending of the distal end of the rail, therebybending the rail in a particular direction. In preferred embodiments,the rail has more than one bend along its length, thereby providingmultiple directions of bending. As the rail is bent, it presses againstthe other assemblies to bend them as well, and thus the other assembliesof the delivery system 10 can be configured to steer along with the railas a cooperating single unit, thus providing for full steerability ofthe distal end of the delivery system.

Once the rail is steered into a particular location in a patient's body,the prosthesis 100 can be advanced along or relative to the rail throughthe movement of the other sheaths/shafts relative to the rail andreleased into the body. For example, the rail can be bent into a desiredposition within the body, such as to direct the prosthesis 100 towardsthe native mitral valve. The other assemblies (e.g., the outer sheathassembly, the mid shaft assembly, the inner assembly, and the nose coneassembly) can passively follow the bends of the rail. Further, the otherassemblies (e.g., the outer sheath assembly, the mid shaft assembly, theinner assembly, and the nose cone assembly) can be advanced together(e.g., relatively together, sequentially with one actuator,simultaneously, almost simultaneously, at the same time, closely at thesame time) relative to the rail while maintaining the prosthesis 100 inthe compressed position without releasing or expanding the prosthesis100 (e.g., within the implant retention area). The other assemblies(e.g., the outer sheath assembly, the mid shaft assembly, the innerassembly, and the nose cone assembly) can be advanced distally orproximally together relative to the rail. In some embodiments, only theouter sheath assembly, mid shaft assembly, and inner assembly areadvanced together over the rail. Thus, the nose cone assembly may remainin the same position. The assemblies can be individually, sequentially,or simultaneously, translated relative to the inner assembly in order torelease the implant 100 from the implant retention area.

In some embodiments, the outer sheath assembly, the mid shaft assembly,the inner shaft assembly, and the nose cone assembly translate together(e.g., relatively together, sequentially with one actuator,simultaneously, almost simultaneously, at the same time, closely at thesame time). This distal translation can occur while the implant 100remains in a compressed configuration within the implant retention area.

Starting with the outermost assembly, the delivery system 10 can includean outer sheath assembly forming a radially outer covering, or sheath,to surround an implant retention area and prevent the implant fromradially expanding. Specifically, the outer sheath assembly can preventradial expansion of the distal end of the implant from radiallyexpanding. Moving radially inward, the mid shaft assembly can becomposed of a mid shaft hypotube with its distal end attached to anouter retention member or outer retention ring for radially retaining aportion of the prosthesis in a compacted configuration, such as aproximal end of the prosthesis 100. The mid shaft assembly can belocated within a lumen of the outer sheath assembly. Moving furtherinwards, the rail assembly can be configured for steerability, asmentioned above and further described below. The rail assembly can belocated within a lumen of the mid shaft assembly. Moving furtherinwards, the inner shaft assembly can be composed of an inner shaft withits distal end attached to inner retention member or inner retentionring (such as a PEEK ring) for axially retaining the prosthesis, forexample the proximal end of the prosthesis. The inner shaft assembly canbe located within a lumen of the rail assembly. Further, the mostradially-inward assembly is the nose cone assembly which includes thenose cone shaft having its distal end connected to the nose cone. Thenose cone can have a tapered tip. The nose cone assembly is preferablylocated within a lumen of the inner shaft assembly. The nose coneassembly can include a lumen for a guide wire to pass therethrough.

The shaft assembly 12, and more specifically the nose cone assembly,inner assembly, rail assembly, mid shaft assembly, and outer sheathassembly, can be collectively configured to deliver a prosthesis 100positioned within the implant retention area to a treatment location.One or more of the subassemblies can then be moved to allow theprosthesis 100 to be released at the treatment location. For example,one or more of the subassemblies may be movable with respect to one ormore of the other subassemblies. The handle 14 can include variouscontrol mechanisms that can be used to control the movement of thevarious subassemblies as will also be described in more detail below. Inthis way, the prosthesis 100 can be controllably loaded onto thedelivery system 10 and then later deployed within the body. Further, thehandle 14 can provide steering to the rail assembly, providing forbending/flexing/steering of the distal end of the delivery system 10.

The inner retention member, the outer retention ring, and the outersheath assembly can cooperate to hold the prosthesis 100 in a compactedconfiguration. The inner retention member can engage struts (for example132 a/132 b) at the proximal end of the prosthesis 100 in FIG. 2. Forexample, slots located between radially extending teeth on the innerretention member can receive and engage the struts which may end inmushroom-shaped tabs on the proximal end of the prosthesis 100. The midshaft assembly can be positioned over the inner retention member so thatthe first end of the prosthesis 100 is trapped between the innerretention member and the outer retention ring, thereby securelyattaching it to the delivery system 10 between the mid shaft assemblyand the inner retention member. The outer sheath assembly can bepositioned to cover the second end of the prosthesis 100.

The outer retention member may be attached to a distal end of the midshaft hypotube which can in turn be attached to a proximal tube at aproximal end, which in turn can be attached at a proximal end to thehandle 14. The outer retention member can provide further stability tothe prosthesis 100 when in the compressed position. The outer retentionmember can be positioned over the inner retention member so that theproximal end of the prosthesis 100 is trapped therebetween, securelyattaching it to the delivery system 10. The outer retention member canencircle a portion of the prosthesis 100, in particular the first end,thus preventing the prosthesis 100 from expanding. Further, the midshaft assembly can be translated proximally with respect to the innerassembly into the outer sheath assembly, thus exposing a first end ofthe prosthesis 100 held within the outer retention member. In this waythe outer retention member can be used to help secure a prosthesis 100to or release it from the delivery system 10. The outer retention membercan have a cylindrical or elongate tubular shape, and may be referred toas an outer retention ring, though the particular shape is not limiting.

The mid shaft hypotube itself can be made of, for example, high densitypolyethylene (HDPE), as well as other appropriate materials as describedherein. The mid shaft hypotube can be formed of a longitudinallypre-compressed HDPE tube, which can provide certain benefits. Forexample, the pre-compressed HDPE tube can apply a force distally ontothe outer retention member, thus preventing accidental, inadvertent,and/or premature release of the prosthesis 100. Specifically, the distalforce by the mid shaft hypotube keeps the distal end of the outerretention member distal to the inner retention member, thus preventingthe outer retention member from moving proximal to the inner retentionmember before it is desired by a user to release the prosthesis 100.This can remain true even when the delivery system 10 is bent/deflectedat a sharp angle. Further disclosure for the outer retention member andmid shaft hypotube can be found in U.S. Pat. Pub. No. 2016/0317301,hereby incorporated by reference in its entirety.

In the compressed position, the inner frame anchoring features 124 canbe located in a delivered configuration where the inner frame anchoringfeatures 124 point generally distally. The inner frame anchoringfeatures 124 can be restrained in this delivered configuration by theouter sheath assembly. Accordingly, when the outer sheath is withdrawnproximally, the inner frame anchoring features 124 can flip positions(e.g., bend approximately 180 degrees) to a deployed configuration(e.g., pointing generally proximally). In other embodiments, the innerframe anchoring features 124 can be held to point generally proximallyin the delivered configuration and compressed against the body of theprosthesis frame.

The delivery system 10 may be provided to users with a prosthesis 100preinstalled. In other embodiments, the prosthesis 100 can be loadedonto the delivery system shortly before use, such as by a physician ornurse.

Valve Delivery Positioning

Methods of using the delivery system 10 in connection with a replacementmitral valve will now be described. In particular, the delivery system10 can be used in a method for percutaneous delivery of a replacementmitral valve to treat patients with moderate to severe mitralregurgitation. The below methods are merely examples of the how thedelivery system may be used. It will be understood that the deliverysystems described herein can be used as part of other methods as well.

As shown in FIG. 32, in one embodiment the delivery system 10 can beplaced in the ipsilateral femoral vein 1074 and advanced toward theright atrium 1076. A transseptal puncture using known techniques canthen be performed to obtain access to the left atrium 1078. The deliverysystem 10 can then be advanced in to the left atrium 1078 and then tothe left ventricle 1080. FIG. 32 shows the delivery system 10 extendingfrom the ipsilateral femoral vein 1074 to the left atrium 1078. Inembodiments of the disclosure, a guide wire is not necessary to positionthe delivery system 10 in the proper position, although in otherembodiments, one or more guide wires may be used.

Accordingly, it can be advantageous for a user to be able to steer thedelivery system 10 through the complex areas of the heart in order toposition a replacement mitral valve in line with the native mitralvalve. This task can be performed with or without the use of a guidewire with the above disclosed system. The distal end of the deliverysystem can be advanced into the left atrium 1078. A user can thenmanipulate the rail assembly to target the distal end of the deliverysystem 10 to the appropriate area. A user can then continue to pass thebent delivery system 10 through the transseptal puncture and into theleft atrium 1078. A user can then further manipulate the delivery system10 to create an even greater bend in the rail assembly. Further, a usercan torque the entire delivery system 10 to further manipulate andcontrol the position of the delivery system 10. In the fully bentconfiguration, a user can then place the replacement mitral valve in theproper location. This can advantageously allow delivery of a replacementvalve to an in-situ implantation site, such as a native mitral valve,via a wider variety of approaches, such as a transseptal approach.

The rail assembly can be particularly advantageous for entering into thenative mitral valve. As discussed above, the rail assembly can form twobends, both of which can be located in the left atrium 1078. The bendsin the rail assembly can position the prosthesis (such as any of thedesigns disclosed above) so that it is coaxial with the native mitralvalve. Once the prosthesis is coaxial, the outer sheath assembly, midshaft assembly, inner assembly, and nose cone assembly can together beadvanced (e.g., using a depth knob of a handle) distally relative to therail assembly. These assemblies advance straight off of the railassembly, thus advancing them coaxial with the native mitral valve untilthe prosthesis is to be released while maintain the prosthesis in thecompressed configuration, as discussed below.

Reference is now made to FIG. 33 which illustrates a schematicrepresentation of a portion of an embodiment of a replacement heartvalve 100 positioned within a native mitral valve of a heart 83. Furtherdetails regarding how the prosthesis may be positioned at the nativemitral valve are described in U.S. Publication No. 2015/0328000A1, theentirety of which is hereby incorporated by reference, including but notlimited to FIGS. 13A-15 and paragraphs [0036]-[0045]. A portion of thenative mitral valve is shown schematically and represents typicalanatomy, including a left atrium positioned above an annulus 1106 and aleft ventricle positioned below the annulus 1106. The left atrium andleft ventricle communicate with one another through a mitral annulus1106. Also shown schematically in FIG. 33 is a native mitral leaflet1108 having chordae tendineae 1110 that connect a downstream end of themitral leaflet 1108 to the papillary muscle of the left ventricle 1080.The portion of the prosthesis 100 disposed upstream of the annulus 1106(toward the left atrium) can be referred to as being positionedsupra-annularly. The portion generally within the annulus 1106 isreferred to as positioned intra-annularly. The portion downstream of theannulus 1106 is referred to as being positioned sub-annularly (towardthe left ventricle).

As shown in FIG. 33, the replacement heart valve (e.g., prosthesis 100)can be positioned so that the mitral annulus 1106 is located above theinner frame anchoring features 124. In some situations, the prosthesis100 can be positioned such that ends or tips of the inner frameanchoring features 124 contact the annulus 1106 as shown, for example,in FIG. 33. In some situations, the prosthesis 100 can be positionedsuch that ends or tips of the inner frame anchoring features 124 do notcontact the annulus 1106. In some situations, the prosthesis 100 can bepositioned such that the inner frame anchoring features 124 do notextend around the leaflet 1108.

As illustrated in FIG. 33, the replacement heart valve 70 can bepositioned so that the ends or tips of the inner frame anchoringfeatures 124 are on a ventricular side of the mitral annulus 1106. Theinner frame anchoring features 124 can be positioned such that the endsor tips of the inner frame anchoring features 124 are on a ventricularside of the native leaflets beyond a location where chordae tendineae1110 connect to free ends of the native leaflets. The inner frameanchoring features 124 may extend between at least some of the chordaetendineae 1110 and, in some situations such as those shown in FIG. 33,can contact or engage a ventricular side of the annulus 1106. It is alsocontemplated that in some situations, the inner frame anchoring features124 may not contact the annulus 1106, though the inner frame anchoringfeatures 124 may still contact the native leaflet 1108. In somesituations, the inner frame anchoring features 124 can contact tissue ofthe left ventricle 104 beyond the annulus 1106 and/or a ventricular sideof the leaflets.

During delivery, the inner frame anchoring features 124 (along with theframe) can be moved toward the ventricular side of the annulus 1106,such as by translating the other assemblies proximally with respect tothe rail assembly, with the inner frame anchoring features 124 extendingbetween at least some of the chordae tendineae 1110 to provide tensionon the chordae tendineae 1110. The degree of tension provided on thechordae tendineae 1110 can differ. For example, little to no tension maybe present in the chordae tendineae 1110 where the leaflet 1108 isshorter than or similar in size to the inner frame anchoring features124. A greater degree of tension may be present in the chordae tendineae1110 where the leaflet 1108 is longer than the inner frame anchoringfeatures 124 and, as such, takes on a compacted form and is pulledproximally. An even greater degree of tension may be present in thechordae tendineae 1110 where the leaflets 1108 are even longer relativeto the inner frame anchoring features 124. The leaflet 1108 can besufficiently long such that the inner frame anchoring features 124 donot contact the annulus 1106.

As discussed above, the prosthesis 100 may not include an outer frameanchoring feature. However, some embodiments such as shown in FIG. 12may include the outer frame anchoring feature 144. The outer frameanchoring feature 144, if present, can be positioned such that the endsor tips of the outer frame anchoring feature 144 are adjacent the atrialside of the annulus 1106 and/or tissue of the left atrium beyond theannulus 1106. In some situations, some or all of the outer frameanchoring feature 144 may only occasionally contact or engage atrialside of the annulus 1106 and/or tissue of the left atrium 1078 beyondthe annulus 1106. For example, the outer frame anchoring feature 144 maybe spaced from the atrial side of the annulus 1106 and/or tissue of theleft atrium beyond the annulus 1106. The outer frame anchoring feature144 could provide axial stability for the prosthesis 100. It is alsocontemplated that some or all of the outer frame anchoring feature 144may contact the atrial side of the annulus 1106 and/or tissue of theleft atrium beyond the annulus 1106. FIG. 34 illustrates the prosthesis100 implanted in the heart 83. Although the illustrated replacementheart valve includes both proximal and distal anchors, it will beappreciated that proximal and distal anchors are not required in allcases. For example, a replacement heart valve with only distal anchorsmay be capable of securely maintaining the replacement heart valve inthe annulus. This is because the largest forces on the replacement heartvalve are directed toward the left atrium during systole. As such, thedistal anchors are most important for anchoring the replacement heartvalve in the annulus and preventing migration.

From the foregoing description, it will be appreciated that an inventiveproduct and approaches for implantable prostheses are disclosed. Whileseveral components, techniques and aspects have been described with acertain degree of particularity, it is manifest that many changes can bemade in the specific designs, constructions and methodology herein abovedescribed without departing from the spirit and scope of thisdisclosure.

Certain features that are described in this disclosure in the context ofseparate implementations can also be implemented in combination in asingle implementation. Conversely, various features that are describedin the context of a single implementation can also be implemented inmultiple implementations separately or in any suitable subcombination.Moreover, although features may be described above as acting in certaincombinations, one or more features from a claimed combination can, insome cases, be excised from the combination, and the combination may beclaimed as any subcombination or variation of any subcombination.

Moreover, while methods may be depicted in the drawings or described inthe specification in a particular order, such methods need not beperformed in the particular order shown or in sequential order, and thatall methods need not be performed, to achieve desirable results. Othermethods that are not depicted or described can be incorporated in theexample methods and processes. For example, one or more additionalmethods can be performed before, after, simultaneously, or between anyof the described methods. Further, the methods may be rearranged orreordered in other implementations. Also, the separation of varioussystem components in the implementations described above should not beunderstood as requiring such separation in all implementations, and itshould be understood that the described components and systems cangenerally be integrated together in a single product or packaged intomultiple products. Additionally, other implementations are within thescope of this disclosure.

Conditional language, such as “can,” “could,” “might,” or “may,” unlessspecifically stated otherwise, or otherwise understood within thecontext as used, is generally intended to convey that certainembodiments include or do not include, certain features, elements,and/or steps. Thus, such conditional language is not generally intendedto imply that features, elements, and/or steps are in any way requiredfor one or more embodiments.

Conjunctive language such as the phrase “at least one of X, Y, and Z,”unless specifically stated otherwise, is otherwise understood with thecontext as used in general to convey that an item, term, etc. may beeither X, Y, or Z. Thus, such conjunctive language is not generallyintended to imply that certain embodiments require the presence of atleast one of X, at least one of Y, and at least one of Z.

Language of degree used herein, such as the terms “approximately,”“about,” “generally,” and “substantially” as used herein represent avalue, amount, or characteristic close to the stated value, amount, orcharacteristic that still performs a desired function or achieves adesired result. For example, the terms “approximately”, “about”,“generally,” and “substantially” may refer to an amount that is withinless than or equal to 10% of, within less than or equal to 5% of, withinless than or equal to 1% of, within less than or equal to 0.1% of, andwithin less than or equal to 0.01% of the stated amount. If the statedamount is 0 (e.g., none, having no), the above recited ranges can bespecific ranges, and not within a particular % of the value. Forexample, within less than or equal to 10 wt./vol. % of, within less thanor equal to 5 wt./vol. % of, within less than or equal to 1 wt./vol. %of, within less than or equal to 0.1 wt./vol. % of, and within less thanor equal to 0.01 wt./vol. % of the stated amount.

Some embodiments have been described in connection with the accompanyingdrawings. The figures are drawn to scale, but such scale should not belimiting, since dimensions and proportions other than what are shown arecontemplated and are within the scope of the disclosed inventions.Distances, angles, etc. are merely illustrative and do not necessarilybear an exact relationship to actual dimensions and layout of thedevices illustrated. Components can be added, removed, and/orrearranged. Further, the disclosure herein of any particular feature,aspect, method, property, characteristic, quality, attribute, element,or the like in connection with various embodiments can be used in allother embodiments set forth herein. Additionally, it will be recognizedthat any methods described herein may be practiced using any devicesuitable for performing the recited steps.

While a number of embodiments and variations thereof have been describedin detail, other modifications and methods of using the same will beapparent to those of skill in the art. Accordingly, it should beunderstood that various applications, modifications, materials, andsubstitutions can be made of equivalents without departing from theunique and inventive disclosure herein or the scope of the claims.

What is claimed is:
 1. A method of replacing a native mitral valve, themethod comprising: advancing a delivery catheter through a patient'svasculature, the delivery catheter having a replacement valve prosthesisdisposed along a distal end portion thereof and configured to transitionbetween a compressed configuration and an expanded configuration,wherein the replacement valve prosthesis comprises: an inner framehaving an hourglass shape when the prosthesis is in the expandedconfiguration; an outer frame connected to the inner frame, wherein,when the prosthesis is in the expanded configuration, a longitudinallength of the outer frame overlaps with at least an intermediate regionof the inner frame; a valve body coupled to a curved interior surface ofthe inner frame formed by the hourglass shape of the inner frame, thevalve body comprising a plurality of leaflets arranged to allow bloodflow in a first direction and prevent blood flow in a second directionopposite the first direction, wherein, when the prosthesis is in theexpanded configuration and the valve body is in the open configuration,the leaflets are adapted to have a longitudinal curvature that followsthe curved hourglass shape of the inner frame such that the leafletsconform to and lie flush against the curved interior surface of theinner frame; releasing the prosthesis from the delivery catheter so thatthe prosthesis expands from the compressed configuration to the expandedconfiguration within the native mitral valve; and removing the deliverycatheter from the patient's vasculature.
 2. The method of claim 1,wherein, when the valve body is in the open configuration, only a freeedge at a distal end of each of the leaflets does not contact the innerframe.
 3. The method of claim 1, wherein an upper region of the innerframe and an upper region of the outer frame each comprisescorresponding eyelets, and wherein the inner frame and the outer frameare attached via the corresponding eyelets of the inner frame and theouter frame.
 4. The method of claim 1, wherein, when the prosthesis isin the expanded configuration and when the valve body is in the openconfiguration, an intermediate portion of a longitudinal length of eachof the leaflets contacts a waist of the intermediate region of the innerframe.
 5. The method of claim 1, wherein the inner frame furthercomprises a plurality of inner frame anchoring features extendingradially outwardly and then proximally toward a proximal end of theprosthesis when the prosthesis is in the expanded configuration.
 6. Themethod of claim 1, wherein the outer frame has a bulbous shape.
 7. Themethod of claim 1, wherein the outer frame comprises a circumferentialshoulder spaced from a proximal end of the outer frame and the distalend of the outer frame, the circumferential shoulder being a radiallyoutermost portion of the outer frame.
 8. The method of claim 1, whereinthe prosthesis further comprises a fabric skirt connected to an outersurface of a distal end of the inner frame.
 9. The method of claim 8,wherein the fabric skirt is held in tension between the outer frame andthe inner frame.
 10. A method of replacing a native mitral valve, themethod comprising: advancing a delivery catheter through a patient'svasculature, the delivery catheter having a replacement valve prosthesisdisposed along a distal end portion thereof and configured to transitionbetween a compressed configuration and an expanded configuration,wherein the replacement valve prosthesis comprises: an inner framecomprising an upper region, an intermediate region, and a lower region,wherein, when the prosthesis is in the expanded configuration, theintermediate region has a narrower diameter than both the upper regionand the lower region so as to form an interior surface that tapersradially inward from the upper region toward the intermediate region andtapers radially outward from the intermediate region to the lowerregion; an outer frame connected to the inner frame, wherein, when theprosthesis is in the expanded configuration, at least the intermediateregion of the inner frame is positioned radially within a portion of alength of the outer frame; and a valve body connected along the interiorsurface of the inner frame, the valve body comprising a plurality ofleaflets arranged to allow blood flow in a first direction and preventblood flow in a second direction, wherein, when the prosthesis is in theexpanded configuration, each of the leaflets has a longitudinalcurvature that conforms to the interior surface of the inner frame;releasing at least a portion of the prosthesis from the deliverycatheter so that the prosthesis expands from the compressedconfiguration to the expanded configuration within the native mitralvalve; and removing the delivery catheter from the patient'svasculature.
 11. The method of claim 10, wherein the upper region of theinner frame and an upper region of the outer frame each comprisescorresponding eyelets, and wherein the inner frame and the outer frameare coupled together via the corresponding eyelets of the inner frameand the outer frame.
 12. The method of claim 10, wherein, when theprosthesis is in the expanded configuration and when the valve body isin the open configuration, an intermediate portion of a longitudinallength of each of the leaflets contacts a waist of the intermediateregion of the inner frame.
 13. The method of claim 10, wherein the outerframe comprises a circumferential shoulder spaced from a proximal end ofthe outer frame and a distal end of the outer frame, the circumferentialshoulder being a radially outermost portion of the outer frame.
 14. Themethod of claim 10, wherein over 90% of a longitudinal length of each ofthe leaflets contacts the interior surface of the inner frame when thevalve body is in the open configuration.
 15. The method of claim 10,wherein only a free edge at a distal end of each of the leaflets doesnot contact the inner frame when the valve body is in the openconfiguration.
 16. A method of replacing a native heart valve, themethod comprising: advancing a delivery catheter through a patient'svasculature, the delivery catheter having a replacement valve prosthesisdisposed along a distal end portion thereof and configured to transitionbetween a compressed configuration and an expanded configuration,wherein the replacement valve prosthesis comprises: an inner framecomprising an upper region, an intermediate region, and a lower region,wherein the intermediate region has a smaller diameter than the upperregion and the lower region so as to form a first curved interiorsurface extending from the upper region to the intermediate region and asecond curved interior surface extending from the lower region to theintermediate region; an outer frame connected to the inner frame, and avalve body positioned within the inner frame, the valve body comprisinga plurality of leaflets arranged to allow blood flow in a firstdirection and prevent blood flow in a second direction, wherein, whenthe prosthesis is in the expanded configuration and the valve body is inan open configuration, a longitudinal length of each leaflet is adaptedto have a final curvature that conforms to the curved interior surfaceof the inner frame; releasing at least a portion of the prosthesis fromthe delivery catheter so that the prosthesis expands from the compressedconfiguration to the expanded configuration within the native heartvalve; and removing the delivery catheter from the patient'svasculature.
 17. The method of claim 16, wherein the native heart valveis a mitral valve.
 18. The method of claim 16, wherein the native heartvalve is a tricuspid valve.
 19. The method of claim 16, wherein over 90%of the longitudinal length of each leaflet contacts at least one of thefirst and second curved interior surfaces of the inner frame when thevalve body is in the open configuration.
 20. The method of claim 16,wherein only a free edge at a distal end of each of the plurality ofleaflets does not contact the inner frame when the valve body is in theopen configuration.